@article{MTMT:34312618, title = {High-efficiency expression of a novel antimicrobial peptide I20 with superior bactericidal ability and biocompatibility in Pichia pastoris and its efficiency enhancement to aquaculture}, url = {https://m2.mtmt.hu/api/publication/34312618}, author = {Huo, Xingchen and Wang, Pengxu and Zhao, Fengxia and Liu, Qian and Yang, Chunrong and Zhang, Yongan and Su, Jianguo}, doi = {10.1016/j.aquaculture.2023.740149}, journal-iso = {AQUACULTURE}, journal = {AQUACULTURE}, volume = {579}, unique-id = {34312618}, issn = {0044-8486}, abstract = {One of the major constraints on aquaculture is the susceptibility of farmed fish to diseases or slow growing. Antimicrobial peptide I20, as a novel feed additive, is used to cope with these limiting factors. In the current study, the Pichia pastoris expression system was used to produce I20 in large quantities, thereby reducing its application cost. In terms of molecular strategy, the I20 expression codon was optimized according to the preference of P. pastoris codon. Through traditional strategy optimization (expression strain, time, methanol concentration, temperature, and pH), the expression level of I20 in shaking bottles was 21.09 +/- 1.10 mg/L. Surprisingly, the expression level of I20 in a 20 L high-cell-density cultivation was 514.78 +/- 22.07 mg/L after methanol induction of 72 h. Comprehensive analyses using a series of fluorescence and microscopy revealed that I20 killed bacteria by increasing bacterial membrane permeability and binding bacterial DNA. I20 effectively killed a variety of pathogenic bacteria (Aeromonas hydrophila, Aeromonas veronii, Elizabethkingia miricola, Fla-vobacterium columnare, Edwardsiella ictaluri, Vibrio parahaemolyticus, Streptococcus agalactiae, Nocardia seriolae, Escherichia coli, and Staphylococcus aureus). I20 was found to have excellent biocompatibility after both feeding and injection studies. Grass carp were fed I20 diet supplemented with 200 mg/Kg I20 for 8 weeks. I20 can effectively promote intestinal villus length, secretion of digestive enzymes, and expression of growth genes to improve growth performance. I20 significantly promotes immune response to reduce tissue damage and bacterial load, enhancing survival after Aeromonas hydrophila infection. In conclusion, we systematically optimized the expression of antimicrobial peptide I20 in P. pastoris, and achieved a satisfactory efficiency for producing antimicrobial peptide I20 by integrating several strategies. The results herein showed that I20-feed promoted growth performance and disease resistance in fish, suggesting a feed supplement with great potential applica-tions for aquaculture.}, keywords = {biocompatibility; Yeast expression; Antimicrobial peptide; Growth performance; Anti-bacterial infection}, year = {2024}, eissn = {1873-5622} } @article{MTMT:34628118, title = {Antimicrobial properties of tomato juice and peptides against typhoidal Salmonella}, url = {https://m2.mtmt.hu/api/publication/34628118}, author = {Kwon, Ryan S. and Lee, Gi Young and Lee, Sohyoung and Song, Jeongmin}, doi = {10.1128/spectrum.03102-23}, journal-iso = {MICROBIOL SPEC}, journal = {MICROBIOLOGY SPECTRUM}, unique-id = {34628118}, issn = {2165-0497}, keywords = {TOMATO; ANTIMICROBIAL PEPTIDES; Salmonella; Gram-negative bacteria; Antimicrobials; enteric pathogens}, year = {2024}, eissn = {2165-0497} } @article{MTMT:34524605, title = {Discovery of an adjuvant that resensitizes polymyxin B-resistant bacteria}, url = {https://m2.mtmt.hu/api/publication/34524605}, author = {Mahdavi, Michael and Findlay, Brandon L.}, doi = {10.1016/j.bmc.2023.117541}, journal-iso = {BIOORGAN MED CHEM}, journal = {BIOORGANIC & MEDICINAL CHEMISTRY}, volume = {97}, unique-id = {34524605}, issn = {0968-0896}, year = {2024}, eissn = {1464-3391}, orcid-numbers = {Findlay, Brandon L./0000-0001-7083-2513} } @article{MTMT:34628115, title = {Engineered Peptides Harboring Cation Motifs Against Multidrug-Resistant Bacteria}, url = {https://m2.mtmt.hu/api/publication/34628115}, author = {Shang, Lu and Chen, Chan and Sun, Rui and Guo, Juan and Liu, Jing and Wang, Mi and Zhang, Lifang and Fei, Chenzhong and Xue, Feiqun and Liu, Yingchun and Gu, Feng}, doi = {10.1021/acsami.3c15913}, journal-iso = {ACS APPL MATER INTER}, journal = {ACS APPLIED MATERIALS & INTERFACES}, volume = {16}, unique-id = {34628115}, issn = {1944-8244}, keywords = {Biofilm; Antibiotic resistance; Antimicrobial peptide; biosafety; multidrug-resistant pathogens}, year = {2024}, eissn = {1944-8252}, pages = {5522-5535} } @article{MTMT:34628116, title = {Escherichia coli resistance mechanism AcrAB-TolC efflux pump interactions with commonly used antibiotics: a molecular dynamics study}, url = {https://m2.mtmt.hu/api/publication/34628116}, author = {Smith, Brooke L. and Fernando, Sandun and King, Maria D.}, doi = {10.1038/s41598-024-52536-z}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {14}, unique-id = {34628116}, issn = {2045-2322}, year = {2024}, eissn = {2045-2322} } @article{MTMT:34628119, title = {Electrochemical degradation of ciprofloxacin from water: Modeling and prediction using ANN and LSSVM}, url = {https://m2.mtmt.hu/api/publication/34628119}, author = {Abbasi, Pezhman and Moghadam, Ehsan Bahrami}, doi = {10.1016/j.pce.2023.103509}, journal-iso = {PHYS CHEM EARTH (2002-)}, journal = {PHYSICS AND CHEMISTRY OF THE EARTH (2002-)}, volume = {132}, unique-id = {34628119}, issn = {1474-7065}, keywords = {ciprofloxacin; ANN; water pollution; Electrochemical degradation; LSSVM; BDD anode}, year = {2023}, eissn = {1873-5193} } @article{MTMT:34523041, title = {A comprehensive guide on screening and selection of a suitable AMP against biofilm-forming bacteria}, url = {https://m2.mtmt.hu/api/publication/34523041}, author = {Anurag, Anand A. and Amod, A. and Anwar, S. and Sahoo, A.K. and Sethi, G. and Samanta, S.K.}, doi = {10.1080/1040841X.2023.2293019}, journal-iso = {CRIT REV MICROBIOL}, journal = {CRITICAL REVIEWS IN MICROBIOLOGY}, unique-id = {34523041}, issn = {1040-841X}, abstract = {Lately, antimicrobial resistance (AMR) is increasing at an exponential rate making it important to search alternatives to antibiotics in order to combat multi-drug resistant (MDR) bacterial infections. Out of the several antibacterial and antibiofilm strategies being tested, antimicrobial peptides (AMPs) have shown to give better hopes in terms of a long-lasting solution to the problem. To select a desired AMP, it is important to make right use of available tools and databases that aid in identification, classification, and analysis of the physiochemical properties of AMPs. To identify the targets of these AMPs, it becomes crucial to understand their mode-of-action. AMPs can also be used in combination with other antibacterial and antibiofilm agents so as to achieve enhanced efficacy against bacteria and their biofilms. Due to concerns regarding toxicity, stability, and bioavailability, strategizing drug formulation at an early-stage becomes crucial. Although there are few concerns regarding development of bacterial resistance to AMPs, the evolution of resistance to AMPs occurs extremely slowly. This comprehensive review gives a deep insight into the selection of the right AMP, deciding the right target and combination strategy along with the type of formulation needed, and the possible resistance that bacteria can develop to these AMPs. © 2023 Informa UK Limited, trading as Taylor & Francis Group.}, keywords = {ANTIBACTERIAL; antibiotics; ANTIMICROBIAL PEPTIDES; ANTIMICROBIAL RESISTANCE; Antibiofilm}, year = {2023}, eissn = {1549-7828} } @article{MTMT:34770447, title = {Mechanism of lipid bilayer perturbation by bactericidal membrane-active small molecules}, url = {https://m2.mtmt.hu/api/publication/34770447}, author = {Bortolotti, A. and Troiano, C. and Bobone, S. and Konai, M. M. and Ghosh, C. and Bocchinfuso, G. and Acharya, Y. and Santucci, V. and Bonacorsi, S. and Di, Stefano C. and Haldar, J. and Stella, L.}, doi = {10.1016/j.bbamem.2022.184079}, journal-iso = {BBA-BIOMEMBRANES}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES}, volume = {1865}, unique-id = {34770447}, issn = {0005-2736}, abstract = {Membrane-active small molecules (MASMs) are small organic molecules designed to reproduce the fundamental physicochemical properties of natural antimicrobial peptides: their cationic charge and amphiphilic character. This class of compounds has a promising broad range of antimicrobial activity and, at the same time, solves some major limitations of the peptides, such as their high production costs and low in vivo stability. Most cationic antimicrobial peptides act by accumulating on the surface of bacterial membranes and causing the formation of defects when a threshold is reached. Due to the drastically different structures of the two classes of molecules, it is not obvious that small-molecule antimicrobials act in the same way as natural peptides, and very few data are available on this aspect. Here we combined spectroscopic studies and molecular dynamics simulations to characterize the mechanism of action of two different MASMs. Our results show that, notwithstanding their simple structure, these molecules act just like antimicrobial peptides. They bind to the membrane surface, below the head-groups, and insert their apolar moieties in the core of the bilayer. Like many natural peptides, they cause the formation of defects when they reach a high coverage of the membrane surface. In addition, they cause membrane aggregation, and this property could contribute to their antimicrobial activity.}, keywords = {PARTITION; SELECTIVITY; FLUORESCENCE; PEPTIDOMIMETICS; PEPTIDOMIMETICS; BIOFILMS; penetration; Fluorescence spectroscopy; molecular dynamics simulations; permeabilization; Biochemistry & Molecular Biology; Thanatin; Host-defense peptide; Small organic antimicrobial molecules; Mechanism of pore formation}, year = {2023}, eissn = {1879-2642} } @article{MTMT:34025037, title = {Very Large Pores Mesoporous Silica as New Candidate for Delivery of Big Therapeutics Molecules, Such as Pharmaceutical Peptides}, url = {https://m2.mtmt.hu/api/publication/34025037}, author = {Carrozza, D. and Malavasi, G. and Ferrari, E.}, doi = {10.3390/ma16114151}, journal-iso = {MATERIALS}, journal = {MATERIALS}, volume = {16}, unique-id = {34025037}, abstract = {The synthesis of a scaffold that can accommodate big molecules with a pharmaceutical role is important to shield them and maintain their biological activity. In this field, silica particles with large pores (LPMS) are innovative supports. Large pores allow for the loading of bioactive molecules inside the structure and contemporarily their stabilization and protection. These purposes cannot be achieved using classical mesoporous silica (MS, pore size 2–5 nm), because their pores are not big enough and pore blocking occurs. LPMSs with different porous structures are synthesized starting from an acidic water solution of tetraethyl orthosilicate reacting with pore agents (Pluronic® F127 and mesitylene), performing hydrothermal and microwave-assisted reactions. Time and surfactant optimization were performed. Loading tests were conducted using Nisin as a reference molecule (polycyclic antibacterial peptide, with dimensions of 4–6 nm); UV-Vis analyses on loading solutions were performed. For LPMSs, a significantly higher loading efficiency (LE%) was registered. Other analyses (Elemental Analysis, Thermogravimetric Analysis and UV-Vis) confirmed the presence of Nisin in all the structures and its stability when loaded on them. LPMSs showed a lower decrease in specific surface area if compared to MS; in terms of the difference in LE% between samples, it is explained considering the filling of pores for LPMSs, a phenomenon that is not allowed for MSs. Release studies in simulated body fluid highlight, only for LPMSs, a controlled release, considering the longer time scale of release. Scanning Electron Microscopy images acquired before and after release tests shows the LPMSs’ maintenance of the structure, demonstrating strength and mechanical resistance of structures. In conclusion, LPMSs were synthesized, performing time and surfactant optimization. LPMSs showed better loading and releasing properties with respect to classical MS. All collected data confirm a pore blocking for MS and an in-pore loading for LPMS. © 2023 by the authors.}, keywords = {PEPTIDES; SILICA; MOLECULES; scanning electron microscopy; Drug delivery; antibiotics; Particle size analysis; Surface active agents; Synthesis (chemical); Thermogravimetric analysis; Body fluids; Mesoporous materials; Large pores; Optimisations; Pore size; BIOACTIVITY; MESOPOROUS SILICAS; Loading efficiency; nisin; nisin; Pore blocking; Synthesised; Porous biomaterials; large pores’ mesoporous silica; pharmaceutical peptides; pharmaceutical peptides; Large pore’ mesoporous silicum; Porous biomaterial}, year = {2023}, eissn = {1996-1944} } @article{MTMT:34126802, title = {Mechanisms of low susceptibility to the disinfectant benzalkonium chloride in a multidrug-resistant environmental isolate of Aeromonas hydrophila}, url = {https://m2.mtmt.hu/api/publication/34126802}, author = {Chacón, L. and Kuropka, B. and González-Tortuero, E. and Schreiber, F. and Rojas-Jiménez, K. and Rodríguez-Rojas, A.}, doi = {10.3389/fmicb.2023.1180128}, journal-iso = {FRONT MICROBIOL}, journal = {FRONTIERS IN MICROBIOLOGY}, volume = {14}, unique-id = {34126802}, issn = {1664-302X}, abstract = {Excessive discharge of quaternary ammonium disinfectants such as benzalkonium chloride (BAC) into aquatic systems can trigger several physiological responses in environmental microorganisms. In this study, we isolated a less-susceptible strain of Aeromonas hydrophila to BAC, designated as INISA09, from a wastewater treatment plant in Costa Rica. We characterized its phenotypic response upon exposure to three different concentrations of BAC and characterized mechanisms related to its resistance using genomic and proteomic approaches. The genome of the strain, mapped against 52 different sequenced A. hydrophila strains, consists of approximately 4.6 Mb with 4,273 genes. We found a massive genome rearrangement and thousands of missense mutations compared to the reference strain A. hydrophila ATCC 7966. We identified 15,762 missense mutations mainly associated with transport, antimicrobial resistance, and outer membrane proteins. In addition, a quantitative proteomic analysis revealed a significant upregulation of several efflux pumps and the downregulation of porins when the strain was exposed to three BAC concentrations. Other genes related to membrane fatty acid metabolism and redox metabolic reactions also showed an altered expression. Our findings indicate that the response of A. hydrophila INISA09 to BAC primarily occurs at the envelop level, which is the primary target of BAC. Our study elucidates the mechanisms of antimicrobial susceptibility in aquatic environments against a widely used disinfectant and will help better understand how bacteria can adapt to biocide pollution. To our knowledge, this is the first study addressing the resistance to BAC in an environmental A. hydrophila isolate. We propose that this bacterial species could also serve as a new model to study antimicrobial pollution in aquatic environments. Copyright © 2023 Chacón, Kuropka, González-Tortuero, Schreiber, Rojas-Jiménez and Rodríguez-Rojas.}, keywords = {GENE; ARTICLE; single nucleotide polymorphism; protein analysis; controlled study; nonhuman; dose response; growth rate; DNA sequencing; AQUATIC ENVIRONMENT; PROTEIN FUNCTION; protein expression; minimum inhibitory concentration; Tetracycline; CEFTAZIDIME; multidrug resistance; ciprofloxacin; gentamicin; vancomycin; gene sequence; proteomics; Biofilm; upregulation; fatty acid metabolism; bacterial strain; amoxicillin; bacterium culture; doxycycline; disinfection; bacterial growth; disinfectant agent; biocide; biocide; ampicillin; antibiotic sensitivity; streptomycin; rifampicin; trimethoprim; Antibiotic resistance; benzalkonium chloride; benzalkonium chloride; down regulation; chloramphenicol; disk diffusion; wastewater; missense mutation; Liquid chromatography-Mass spectrometry; colony forming unit; DNA extraction; Aeromonas hydrophila; bacterium isolation; bacterium contamination; Primary response; waste water treatment plant; colistin; 16S rRNA gene; porin; fosfomycin; CRISPR Cas system; daptomycin; Zone of inhibition; concentration (parameter); low-susceptibility; quaternary ammonium disinfectants}, year = {2023}, eissn = {1664-302X} } @article{MTMT:33759558, title = {Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens}, url = {https://m2.mtmt.hu/api/publication/33759558}, author = {Chaudhary, S. and Ali, Z. and Tehseen, M. and Haney, E.F. and Pantoja-Angles, A. and Alshehri, S. and Wang, T. and Clancy, G.J. and Ayach, M. and Hauser, C. and Hong, P.-Y. and Hamdan, S.M. and Hancock, R.E.W. and Mahfouz, M.}, doi = {10.1038/s41467-023-37003-z}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {14}, unique-id = {33759558}, issn = {2041-1723}, abstract = {Antimicrobial peptides (AMPs) are promising next-generation antibiotics that can be used to combat drug-resistant pathogens. However, the high cost involved in AMP synthesis and their short plasma half-life render their clinical translation a challenge. To address these shortcomings, we report efficient production of bioactive amidated AMPs by transient expression of glycine-extended AMPs in Nicotiana benthamiana line expressing the mammalian enzyme peptidylglycine α-amidating mono-oxygenase (PAM). Cationic AMPs accumulate to substantial levels in PAM transgenic plants compare to nontransgenic N. benthamiana. Moreover, AMPs purified from plants exhibit robust killing activity against six highly virulent and antibiotic resistant ESKAPE pathogens, prevent their biofilm formation, analogous to their synthetic counterparts and synergize with antibiotics. We also perform a base case techno-economic analysis of our platform, demonstrating the potential economic advantages and scalability for industrial use. Taken together, our experimental data and techno-economic analysis demonstrate the potential use of plant chassis for large-scale production of clinical-grade AMPs. © 2023, The Author(s).}, keywords = {Animals; PEPTIDE; ENZYME; GENETICS; PLANTS; animal; PLANT; mammal; Drug Resistance; Gene Expression; tobacco; tobacco; antibiotics; antiinfective agent; ANTIMICROBIAL ACTIVITY; ANTIMICROBIAL PEPTIDES; MAMMALS; Biofilm; anti-bacterial agents; phytochemistry; polypeptide antibiotic agent; dicotyledon; Antimicrobial Cationic Peptides; antimicrobial cationic peptide}, year = {2023}, eissn = {2041-1723} } @article{MTMT:33759569, title = {Antimicrobial peptides as promising antibiotic adjuvants to combat drug-resistant pathogens}, url = {https://m2.mtmt.hu/api/publication/33759569}, author = {Chen, C. and Shi, J. and Wang, D. and Kong, P. and Wang, Z. and Liu, Y.}, doi = {10.1080/1040841X.2023.2186215}, journal-iso = {CRIT REV MICROBIOL}, journal = {CRITICAL REVIEWS IN MICROBIOLOGY}, unique-id = {33759569}, issn = {1040-841X}, abstract = {The widespread antimicrobial resistance (AMR) calls for the development of new antimicrobial strategies. Antibiotic adjuvant rescues antibiotic activity and increases the life span of the antibiotics, representing a more productive, timely, and cost-effective strategy in fighting drug-resistant pathogens. Antimicrobial peptides (AMPs) from synthetic and natural sources are considered new-generation antibacterial agents. Besides their direct antimicrobial activity, growing evidence shows that some AMPs effectively enhance the activity of conventional antibiotics. The combinations of AMPs and antibiotics display an improved therapeutic effect on antibiotic-resistant bacterial infections and minimize the emergence of resistance. In this review, we discuss the value of AMPs in the age of resistance, including modes of action, limiting evolutionary resistance, and their designing strategies. We summarise the recent advances in combining AMPs and antibiotics against antibiotic-resistant pathogens, as well as their synergistic mechanisms. Lastly, we highlight the challenges and opportunities associated with the use of AMPs as potential antibiotic adjuvants. This will shed new light on the deployment of synergistic combinations to address the AMR crisis. © 2023 Informa UK Limited, trading as Taylor & Francis Group.}, keywords = {ANTIMICROBIAL PEPTIDES; Antibiotic adjuvant; Drug-resistant pathogens; synergy mechanisms}, year = {2023}, eissn = {1549-7828} } @article{MTMT:34126795, title = {In vitro efficacy and combined drug sensitivity of lycosin-I against methicillin-resistant Staphylococcus aureus}, url = {https://m2.mtmt.hu/api/publication/34126795}, author = {Chen, H. and Wang, L. and Hu, M.}, doi = {10.3760/cma.j.cn114452-20230418-00443}, journal-iso = {CHIN J LAB MED}, journal = {CHINESE JOURNAL OF LABORATORY MEDICINE}, volume = {46}, unique-id = {34126795}, issn = {1009-9158}, abstract = {Objective The aim of this study was to evaluate the in vitro activity of lysosin-Ⅰ against Methicillin-resistant Staphylococcus aureus (MRSA) and its synergistic effect with eight common antibacterial drugs against MRSA. Methods This study was conducted following the design principles of a randomized controlled trials. Ten MRSA isolates, clinically isolated from the Second Xiangya Hospital of Central South University between September and November 2021, were determined the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bactericidal kinetic test of lycosin-Ⅰ in vitro anti-MRSA by micro-broth dilution method. Additionally, the micro-broth chessboard dilution method was utilized to evaluate the in vitro efficacy of lycosin-Ⅰ in combination with eight common antimicrobial agants, including penicillin, erythromycin, levofloxacin, gentamicin, rifampicin, minocycline, vancomycin, and linezolid. Results The MIC range of lycosin-Ⅰ against MRSA was found to be between 4-8 mg/L with the MIC50 and MIC90 were 4 mg/L and 8 mg/L, respectively. The range of MBC was also between 4-8 mg/L, and the ratio of MBC/MIC was 1-2. The bactericidal kinetics test revealed that the number of surviving MRSA clinical isolates and standard strains initially decreased rapidly but then showed a resurgence when the concentration of lycosin-Ⅰ was 1/2 MIC or MIC. While, the bacterial load gradually reduced until complete elimination when the concentration was at 2 MIC or 4 MIC. The combination of lycosin-Ⅰ and gentamicin exhibited mainly synergistic effects, while the combination with other antibiotics showed mainly additive effects. Moreover, the combination of lycosin-Ⅰ and antibacterial drugs can significantly reduce the MIC50 and MIC90 of antibiotics. Conclusion lycosin-Ⅰ has great antibacterial and bactericidal activity against MRSA in vitro with rapid and thorough sterilization effect and it can play a synergistic or additive role when combined with other antibacterial drugs against MRSA in vitro. © 2023 Authors. All rights reserved.}, keywords = {Microbial Sensitivity Tests; Methicillin-resistant Staphylococcus aureus; Antimicrobial Cationic Peptides}, year = {2023}, pages = {604-611} } @article{MTMT:34770442, title = {Bacterial envelope stress responses: Essential adaptors and attractive targets}, url = {https://m2.mtmt.hu/api/publication/34770442}, author = {Cho, Timothy H. S. and Pick, Kat and Raivio, Tracy L.}, doi = {10.1016/j.bbamcr.2022.119387}, journal-iso = {BBA-MOL CELL RES}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH}, volume = {1870}, unique-id = {34770442}, issn = {0167-4889}, abstract = {Millions of deaths a year across the globe are linked to antimicrobial resistant infections. The need to develop new treatments and repurpose of existing antibiotics grows more pressing as the growing antimicrobial resistance pandemic advances. In this review article, we propose that envelope stress responses, the signaling pathways bacteria use to recognize and adapt to damage to the most vulnerable outer compartments of the microbial cell, are attractive targets. Envelope stress responses (ESRs) support colonization and infection by responding to a plethora of toxic envelope stresses encountered throughout the body; they have been co-opted into virulence networks where they work like global positioning systems to coordinate adhesion, invasion, microbial warfare, and biofilm formation. We highlight progress in the development of therapeutic strategies that target ESR signaling proteins and adaptive networks and posit that further characterization of the molecular mechanisms governing these essential niche adaptation machineries will be important for sparking new therapeutic ap-proaches aimed at short-circuiting bacterial adaptation.}, keywords = {BACILLUS-SUBTILIS; Gram-negative bacteria; ANTIMICROBIAL RESISTANCE; SALMONELLA-ENTERICA; UROPATHOGENIC ESCHERICHIA-COLI; Bacterial adaptation; Biochemistry & Molecular Biology; two component system; DEPENDENT ACID RESISTANCE; 2-COMPONENT SYSTEM; VIRULENCE GENE-EXPRESSION; Envelope stress responses; ANTIMICROBIAL PEPTIDES ACTIVATE; WIDE TRANSCRIPTIONAL RESPONSE; CONFERS LYSOZYME RESISTANCE}, year = {2023}, eissn = {1879-2596}, orcid-numbers = {Cho, Timothy H. S./0000-0003-4066-1666; Pick, Kat/0000-0002-7291-5440} } @mastersthesis{MTMT:34524592, title = {Leveraging Systems-level Metabolic Modeling and Machine Learning to Optimize Antibiotic Combination Therapy Design}, url = {https://m2.mtmt.hu/api/publication/34524592}, author = {Chung, Carolina H.}, doi = {10.7302/8201}, unique-id = {34524592}, year = {2023} } @article{MTMT:34235446, title = {Chance Favors the Prepared Genomes: Horizontal Transfer Shapes the Emergence of Antibiotic Resistance Mutations in Core Genes}, url = {https://m2.mtmt.hu/api/publication/34235446}, author = {Coluzzi, Charles and Guillemet, Martin and Mazzamurro, Fanny and Touchon, Marie and Godfroid, Maxime and Achaz, Guillaume and Glaser, Philippe and Rocha, Eduardo P. C.}, doi = {10.1093/molbev/msad217}, journal-iso = {MOL BIOL EVOL}, journal = {MOLECULAR BIOLOGY AND EVOLUTION}, volume = {40}, unique-id = {34235446}, issn = {0737-4038}, abstract = {Bacterial lineages acquire novel traits at diverse rates in part because the genetic background impacts the successful acquisition of novel genes by horizontal transfer. Yet, how horizontal transfer affects the subsequent evolution of core genes remains poorly understood. Here, we studied the evolution of resistance to quinolones in Escherichia coli accounting for population structure. We found 60 groups of genes whose gain or loss induced an increase in the probability of subsequently becoming resistant to quinolones by point mutations in the gyrase and topoisomerase genes. These groups include functions known to be associated with direct mitigation of the effect of quinolones, with metal uptake, cell growth inhibition, biofilm formation, and sugar metabolism. Many of them are encoded in phages or plasmids. Although some of the chronologies may reflect epidemiological trends, many of these groups encoded functions providing latent phenotypes of antibiotic low-level resistance, tolerance, or persistence under quinolone treatment. The mutations providing resistance were frequent and accumulated very quickly. Their emergence was found to increase the rate of acquisition of other antibiotic resistances setting the path for multidrug resistance. Hence, our findings show that horizontal gene transfer shapes the subsequent emergence of adaptive mutations in core genes. In turn, these mutations further affect the subsequent evolution of resistance by horizontal gene transfer. Given the substantial gene flow within bacterial genomes, interactions between horizontal transfer and point mutations in core genes may be a key to the success of adaptation processes.}, keywords = {MUTATIONS; MOBILE GENETIC ELEMENTS; Quinolones; Gene gain and loss; espistatic interactions}, year = {2023}, eissn = {1537-1719}, orcid-numbers = {Coluzzi, Charles/0000-0003-2238-0836} } @article{MTMT:34075925, title = {Bioactive collagen peptides: bibliometric approach and market trends for aquatic sources}, url = {https://m2.mtmt.hu/api/publication/34075925}, author = {Costa, Beatriz de Aquino Marques da and Porto, Ana Lúcia Figueiredo and Oliveira, Vagne de Melo and Porto, Tatiana Souza}, doi = {10.58951/fstoday.2023.17}, journal-iso = {fstoday}, journal = {Food Science Today}, volume = {2}, unique-id = {34075925}, abstract = {The development of the collagen peptides industry is associated with new consumption trends among the population, projected to reach a value of 795 million USD by 2025. Given the relevance of the topic, the present work provides an overview of collagen, its sources, applications, as well as the properties and bioactivities of the peptides formed from its hydrolysis. In addition, a bibliometric analysis was performed to highlight a global overview of publication trends, co-authorship, and co-occurrence of keywords. Bibliometric data were obtained from the Web of Science platform using the descriptors “marine collagen peptide,” “marine collagen peptides,” “aquatic collagen peptide,” “aquatic collagen peptides,” “marine collagen hydrolysate,” “marine collagen hydrolysates,” “aquatic collagen hydrolysate” and “aquatic collagen hydrolysates” and the Boolean operator “OR,” to include terms that cover the possible variations used in the search. From the results obtained, articles and reviews published between 2000 and 2021 were selected. From the analysis of the data collected, it became evident the still relatively recent nature of the research on collagen peptides derived from aquatic organisms and the role of countries in Asia and Europe as leaders in the segment. The co-authorship analysis reveals that the collaboration network between authors/institutions is still scarce and strongly restricted to researchers/institutions in the same region. The co-occurrence analysis reveals that most of the works are related to the health area, highlighting its potential in the prevention/treatment of diseases. In view of the results obtained, it is expected that the growth of the production and commercial branch of these peptides will be accompanied by the amplification of collaboration between authors and institutions from different territories, establishing a global network of partnerships.}, year = {2023}, eissn = {2965-1190}, orcid-numbers = {Costa, Beatriz de Aquino Marques da/0000-0001-8742-2959; Porto, Ana Lúcia Figueiredo/0000-0001-5561-5158; Oliveira, Vagne de Melo/0000-0003-0841-1974; Porto, Tatiana Souza/0000-0002-1571-8897} } @article{MTMT:34126798, title = {Role of efflux pumps, their inhibitors, and regulators in colistin resistance}, url = {https://m2.mtmt.hu/api/publication/34126798}, author = {Ding, Y. and Hao, J. and Xiao, W. and Ye, C. and Xiao, X. and Jian, C. and Tang, M. and Li, G. and Liu, J. and Zeng, Z.}, doi = {10.3389/fmicb.2023.1207441}, journal-iso = {FRONT MICROBIOL}, journal = {FRONTIERS IN MICROBIOLOGY}, volume = {14}, unique-id = {34126798}, issn = {1664-302X}, abstract = {Colistin is highly promising against multidrug-resistant and extensively drug-resistant bacteria clinically. Bacteria are resistant to colistin mainly through mcr and chromosome-mediated lipopolysaccharide (LPS) synthesis-related locus variation. However, the current understanding cannot fully explain the resistance mechanism in mcr-negative colistin-resistant strains. Significantly, the contribution of efflux pumps to colistin resistance remains to be clarified. This review aims to discuss the contribution of efflux pumps and their related transcriptional regulators to colistin resistance in various bacteria and the reversal effect of efflux pump inhibitors on colistin resistance. Previous studies suggested a complex regulatory relationship between the efflux pumps and their transcriptional regulators and LPS synthesis, transport, and modification. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), 1-(1-naphthylmethyl)-piperazine (NMP), and Phe-Arg-β-naphthylamide (PAβN) all achieved the reversal of colistin resistance, highlighting the role of efflux pumps in colistin resistance and their potential for adjuvant development. The contribution of the efflux pumps to colistin resistance might also be related to specific genetic backgrounds. They can participate in colistin tolerance and heterogeneous resistance to affect the treatment efficacy of colistin. These findings help understand the development of resistance in mcr-negative colistin-resistant strains. Copyright © 2023 Ding, Hao, Xiao, Ye, Xiao, Jian, Tang, Li, Liu and Zeng.}, keywords = {PHAGOCYTOSIS; POINT MUTATION; LIPOPOLYSACCHARIDE; LIPOPOLYSACCHARIDE; CHROMOSOME; review; human; gene locus; Genetic variability; amino acid substitution; disease predisposition; Escherichia coli; nonhuman; environmental stress; unclassified drug; minimum inhibitory concentration; Tetracycline; RESERPINE; imipenem; cefepime; Serratia marcescens; proteomics; Pseudomonas aeruginosa; salicylic acid; upregulation; teicoplanin; azithromycin; virulence factor; rifampicin; Enterobacter; trimethoprim; cephalosporin; sulfonamide; chloramphenicol; beta lactam; chlorhexidine; macrolide; Salmonella; Polymyxin B; genetic transcription; quinolone; nitrofurantoin; aminoglycoside; efflux pump; efflux pump; Nalidixic Acid; carbonyl cyanide chlorophenylhydrazone; Tigecycline; NODULATION; klebsiella pneumoniae; Neisseria meningitidis; novobiocin; quorum sensing; Efflux pump inhibitors; yersinia enterocolitica; neisseria gonorrhoeae; nitroxoline; Acinetobacter baumannii; Stenotrophomonas maltophilia; type III secretion system; Proteus mirabilis; colistin resistance; colistin resistance; transcription factor ERG; heteroresistance; Enterobacter aerogenes; Burkholderia; aldehyde dehydrogenase isoenzyme 2; phosphoethanolamine; Oxidative stress; multidrug resistant bacterium; pmrH gene; phoP gene; ompf gene; phenylalanine arginine beta naphthylamide; octenidine; collateral susceptibility; 1 (1 naphthylmethyl) piperazine; thiolactamycin; transmembrane transport protein; acrAB gene; bacterial microenvironment; electrochemical gradient depolarization; fumC gene; Mar gene; marA gene; micF gene; phoQ gene; pmrB gene; pmrC gene; pmrD gene; soxRS gene; tolC gene}, year = {2023}, eissn = {1664-302X} } @article{MTMT:34147172, title = {Antimicrobial Peptides (AMP) in the Cell-Free Culture Media of Xenorhabdus budapestensis and X. szentirmaii Exert Anti-Protist Activity against Eukaryotic Vertebrate Pathogens including Histomonas meleagridis and Leishmania donovani Species}, url = {https://m2.mtmt.hu/api/publication/34147172}, author = {Fodor, András and Hess, Claudia and Ganas, Petra and Boros, Zsófia and Kiss, János and Makrai, László and Dublecz, Károly and Pál, László and Fodor, László and Sebestyén, Anna and Klein, Michael G. and Tarasco, Eustachio and Kulkarni, Manjusha M. and McGwire, Bradford S. and Vellai, Tibor and Hess, Michael}, doi = {10.3390/antibiotics12091462}, journal-iso = {ANTIBIOTICS-BASEL}, journal = {ANTIBIOTICS}, volume = {12}, unique-id = {34147172}, abstract = {Anti-microbial peptides provide a powerful toolkit for combating multidrug resistance. Combating eukaryotic pathogens is complicated because the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria (EPB), symbionts of entomopathogenic–nematode species, release a series of non-ribosomal templated anti-microbial peptides. Some may be potential drug candidates. The ability of an entomopathogenic–nematode/entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product. This explains that those gene complexes that are responsible for the biosynthesis of different non-ribosomal templated anti-microbial protective peptides (including those that are potently capable of inactivating the protist mammalian pathogen Leishmania donovanii and the gallinaceous bird pathogen Histomonas meleagridis) are co-regulated. Our approach is based on comparative anti-microbial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated anti-microbial peptides that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourage us to forecast that the recently discovered “easy-PACId” research strategy is suitable for constructing entomopathogenic-bacterium (EPB) strains producing and releasing single, harmless, non-ribosomal templated anti-microbial peptides with considerable drug, (probiotic)-candidate potential.}, year = {2023}, eissn = {2079-6382}, orcid-numbers = {Fodor, András/0000-0003-3495-0154; Hess, Claudia/0000-0002-3535-5157; Kiss, János/0000-0002-0506-5474; Fodor, László/0000-0003-2711-0229; Sebestyén, Anna/0000-0001-8814-4794; Tarasco, Eustachio/0000-0001-6310-186X; Vellai, Tibor/0000-0002-3520-2572} } @article{MTMT:33704277, title = {XENOFOOD—An Autoclaved Feed Supplement Containing Autoclavable Antimicrobial Peptides—Exerts Anticoccidial GI Activity, and Causes Bursa Enlargement, but Has No Detectable Harmful Effects in Broiler Cockerels despite In Vitro Detectable Cytotoxicity on LHM Cells}, url = {https://m2.mtmt.hu/api/publication/33704277}, author = {Fodor, András and Vellai, Tibor and Hess, Claudia and Makrai, László and Dublecz, Károly and Pál, László and Molnár, Andor and Klein, Michael G. and Tarasco, Eustachio and Józsa, Sándor and Ganas, Petra and Hess, Michael}, doi = {10.3390/pathogens12030458}, journal-iso = {PATHOGENS}, journal = {PATHOGENS}, volume = {12}, unique-id = {33704277}, abstract = {Entomopathogenic bacteria are obligate symbionts of entomopathogenic nematode (EPN) species. These bacteria biosynthesize and release non-ribosomal-templated hybrid peptides (NR-AMPs), with strong, and large-spectral antimicrobial potential, capable of inactivating pathogens belonging to different prokaryote, and eukaryote taxa. The cell-free conditioned culture media (CFCM) of Xenorhabdus budapestensis and X. szentirmaii efficiently inactivate poultry pathogens like Clostridium, Histomonas, and Eimeria. To learn whether a bio-preparation containing antimicrobial peptides of Xenorhabdus origin with accompanying (in vitro detectable) cytotoxic effects could be considered a safely applicable preventive feed supplement, we conducted a 42-day feeding experiment on freshly hatched broiler cockerels. XENOFOOD (containing autoclaved X. budapestensis, and X. szentirmaii cultures developed on chicken food) were consumed by the birds. The XENOFOOD exerted detectable gastrointestinal (GI) activity (reducing the numbers of the colony-forming Clostridium perfringens units in the lower jejunum. No animal was lost in the experiment. Neither the body weight, growth rate, feed-conversion ratio, nor organ-weight data differed between the control (C) and treated (T) groups, indicating that the XENOFOOD diet did not result in any detectable adverse effects. We suppose that the parameters indicating a moderate enlargement of bursas of Fabricius (average weight, size, and individual bursa/spleen weight-ratios) in the XENOFOOD-fed group must be an indirect indication that the bursa-controlled humoral immune system neutralized the cytotoxic ingredients of the XENOFOOD in the blood, not allowing to reach their critical cytotoxic concentration in the sensitive tissues.}, year = {2023}, eissn = {2076-0817}, orcid-numbers = {Vellai, Tibor/0000-0002-3520-2572; Hess, Claudia/0000-0002-3535-5157; Tarasco, Eustachio/0000-0001-6310-186X} } @{MTMT:34025065, title = {Antimicrobial peptides: features and modes of action}, url = {https://m2.mtmt.hu/api/publication/34025065}, author = {Francis, F. and Chaudhary, N.}, booktitle = {Antimicrobial Peptides}, doi = {10.1016/B978-0-323-85682-9.00016-7}, unique-id = {34025065}, abstract = {Antimicrobial peptides (AMPs) or host defense peptides are short amphipathic, generally cationic, evolutionarily conserved biomolecules that constitute the first line of defense in most living organisms. These peptides display activity against Gram-negative and Gram-positive bacteria, fungi, and some protozoa and viruses. AMPs can be linear or cyclic; the cyclic structure is achieved through end-to-end ligation or through disulfide bridge(s) between the Cys residues near the termini. Structurally, AMPs can be classified as α-helical, β-sheets, αβ, and non-αβ. Another useful classification could be disulfide-containing and disulfide-lacking peptides. Most AMPs fold into conformations that introduce amphipathicity, a feature that enables them to interact with membranes. Understandably, a large majority of AMPs exhibit antimicrobial activity through membrane-destabilization, which causes leakage of cellular content, thereby causing cell death. Although the exact mechanism of action is an enigma and could be peptide-specific, several models have been proposed for their antimicrobial action. These include the barrel-stave model, the carpet model, the toroidal pore model, and the detergent model. Apart from the antimicrobial activity, AMPs could possess anticancer activity, antimycoplasmal activity, spermicidal activity, cause activation of the immune response, and regulation of inflammation. These attributes of AMPs make them promising candidates as an alternative to conventional antibiotics. © 2023 Elsevier Inc. All rights reserved.}, keywords = {MEMBRANE; ANTIMICROBIAL PEPTIDES; PERTURBATION; Cationic; amphipathic}, year = {2023}, pages = {33-65} } @article{MTMT:33597268, title = {Testing Antimicrobial Properties of Selected Short Amyloids}, url = {https://m2.mtmt.hu/api/publication/33597268}, author = {Gagat, P. and Duda-Madej, A. and Ostrówka, M. and Pietluch, F. and Seniuk, A. and Mackiewicz, P. and Burdukiewicz, M.}, doi = {10.3390/ijms24010804}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {33597268}, issn = {1661-6596}, abstract = {Amyloids and antimicrobial peptides (AMPs) have many similarities, e.g., both kill microorganisms by destroying their membranes, form aggregates, and modulate the innate immune system. Given these similarities and the fact that the antimicrobial properties of short amyloids have not yet been investigated, we chose a group of potentially antimicrobial short amyloids to verify their impact on bacterial and eukaryotic cells. We used AmpGram, a best-performing AMP classification model, and selected ten amyloids with the highest AMP probability for our experimental research. Our results indicate that four tested amyloids: VQIVCK, VCIVYK, KCWCFT, and GGYLLG, formed aggregates under the conditions routinely used to evaluate peptide antimicrobial properties, but none of the tested amyloids exhibited antimicrobial or cytotoxic properties. Accordingly, they should be included in the negative datasets to train the next-generation AMP prediction models, based on experimentally confirmed AMP and non-AMP sequences. In the article, we also emphasize the importance of reporting non-AMPs, given that only a handful of such sequences have been officially confirmed. © 2023 by the authors.}, keywords = {BACTERIA; PREDICTION; machine learning; ANTIMICROBIAL PEPTIDES; amyloids; non-antimicrobial peptides}, year = {2023}, eissn = {1422-0067} } @article{MTMT:33617652, title = {How do antimicrobial peptides disrupt the lipopolysaccharide membrane leaflet of Gram-negative bacteria?}, url = {https://m2.mtmt.hu/api/publication/33617652}, author = {Gong, Haoning and Hu, Xuzhi and Zhang, Lin and Fa, Ke and Liao, Mingrui and Liu, Huayang and Fragneto, Giovanna and Campana, Mario and Lu, Jian Ren}, doi = {10.1016/j.jcis.2023.01.051}, journal-iso = {J COLLOID INTERF SCI}, journal = {JOURNAL OF COLLOID AND INTERFACE SCIENCE}, volume = {637}, unique-id = {33617652}, issn = {0021-9797}, abstract = {It is widely regarded that antimicrobial peptides (AMPs) kill bacteria by phys. disrupting microbial membranes and causing cytoplasmic leakage, but it remains unclear how AMPs disrupt the outer membrane (OM) of Gram-neg. bacteria (GNB) and then compromise the inner membrane. We hypothesise that different AMPs impose different structural disruptions, with direct implications to their antimicrobial efficacies. The antimicrobial activities of three typical AMPs, including the designed short AMP, G3, and two natural AMPs, melittin and LL37, against E. coli and their haemolytic activities were studied. Lipopolysaccharide (LPS) and anionic di-palmitoyl phosphatidyl glycerol (DPPG) monolayer models were constructed to mimic the outer membrane and inner membrane leaflets of Gram-neg. bacteria. The binding and penetration of AMPs to the model lipid monolayers were systematically studied by neutron reflection via multiple H/D contrast variations. G3 has relatively high antimicrobial activity, low cytotoxicity, and high proteolytic stability, while melittin has significant haemolysis and LL37 has weaker antimicrobial activity. G3 could rapidly lyse LPS and DPPG monolayers within 10-20 min. In contrast, melittin was highly active against the LPS membrane, but the dynamic process lasted up to 80 min, with excessive stacking in the OM. LL37 caused rather weak destruction to LPS and DPPG monolayers, leading to massive adsorption on the membrane surface without penetrating the lipid tail region. These findings demonstrate that the rationally designed AMP G3 was well optimized to impose most effective destruction to bacterial membranes, consistent with its highest bactericidal activity. These different interfacial structural features associated with AMP binding shed light on the future development of active and biocompatible AMPs for infection and wound treatments.}, keywords = {LIPOPOLYSACCHARIDE; Antimicrobial peptide; Neutron reflection; Anti-infection; Structural disruption}, year = {2023}, eissn = {1095-7103}, pages = {182-192} } @article{MTMT:33632100, title = {Plasticity and stereotypic rewiring of the transcriptome upon bacterial evolution of antibiotic resistance}, url = {https://m2.mtmt.hu/api/publication/33632100}, author = {Grézal, Gábor and Spohn, Réka and Méhi, Orsolya Katinka and Dunai, Anett and Lázár, Viktória and Bálint, Balázs and Nagy, István and Pál, Csaba and Papp, Balázs}, doi = {10.1093/molbev/msad020}, journal-iso = {MOL BIOL EVOL}, journal = {MOLECULAR BIOLOGY AND EVOLUTION}, volume = {40}, unique-id = {33632100}, issn = {0737-4038}, abstract = {Bacterial evolution of antibiotic resistance frequently has deleterious side effects on microbial growth, virulence, and susceptibility to other antimicrobial agents. However, it is unclear how these trade-offs could be utilized for manipulating antibiotic resistance in the clinic, not least because the underlying molecular mechanisms are poorly understood. Using laboratory evolution, we demonstrate that clinically relevant resistance mutations in Escherichia coli constitutively rewire a large fraction of the transcriptome in a repeatable and stereotypic manner. Strikingly, lineages adapted to functionally distinct antibiotics and having no resistance mutations in common show a wide range of parallel gene expression changes that alter oxidative stress response, iron homeostasis, and the composition of the bacterial outer membrane and cell surface. These common physiological alterations are associated with changes in cell morphology and enhanced sensitivity to antimicrobial peptides. Finally, the constitutive transcriptomic changes induced by resistance mutations are largely distinct from those induced by antibiotic stresses in the wild-type. This indicates a limited role for genetic assimilation of the induced antibiotic stress response during resistance evolution. Our work suggests that diverse resistance mutations converge on similar global transcriptomic states that shape genetic susceptibility to antimicrobial compounds.}, year = {2023}, eissn = {1537-1719}, orcid-numbers = {Grézal, Gábor/0000-0003-1685-4791; Méhi, Orsolya Katinka/0009-0004-7918-913X} } @book{MTMT:34075919, title = {Antimicrobial peptides}, url = {https://m2.mtmt.hu/api/publication/34075919}, author = {Hammond, K and Upton, M and Ryadnov, M}, unique-id = {34075919}, year = {2023} } @article{MTMT:33759556, title = {Tackling antibiotic resistance by inducing transient and robust collateral sensitivity}, url = {https://m2.mtmt.hu/api/publication/33759556}, author = {Hernando-Amado, S. and Laborda, P. and Martínez, J.L.}, doi = {10.1038/s41467-023-37357-4}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {14}, unique-id = {33759556}, issn = {2041-1723}, abstract = {Collateral sensitivity (CS) is an evolutionary trade-off traditionally linked to the mutational acquisition of antibiotic resistance (AR). However, AR can be temporally induced, and the possibility that this causes transient, non-inherited CS, has not been addressed. Mutational acquisition of ciprofloxacin resistance leads to robust CS to tobramycin in pre-existing antibiotic-resistant mutants of Pseudomonas aeruginosa. Further, the strength of this phenotype is higher when nfxB mutants, over-producing the efflux pump MexCD-OprJ, are selected. Here, we induce transient nfxB-mediated ciprofloxacin resistance by using the antiseptic dequalinium chloride. Notably, non-inherited induction of AR renders transient tobramycin CS in the analyzed antibiotic-resistant mutants and clinical isolates, including tobramycin-resistant isolates. Further, by combining tobramycin with dequalinium chloride we drive these strains to extinction. Our results support that transient CS could allow the design of new evolutionary strategies to tackle antibiotic-resistant infections, avoiding the acquisition of AR mutations on which inherited CS depends. © 2023, The Author(s).}, keywords = {metabolism; PHENOTYPE; PHENOTYPE; GENETICS; TRANSCRIPTION FACTOR; transcription factors; ARTICLE; gene mutation; controlled study; nonhuman; Genetic Variation; Microbial Sensitivity Tests; minimum inhibitory concentration; Tetracycline; AMIKACIN; CEFTAZIDIME; CHLORIDE; antiinfective agent; imipenem; ciprofloxacin; ciprofloxacin; ciprofloxacin; gentamicin; Pseudomonas aeruginosa; Pseudomonas aeruginosa; anti-bacterial agents; induced resistance; aztreonam; erythromycin; antibiotic sensitivity; Drug Resistance, Microbial; Antibiotic resistance; Antibiotic resistance; Antibiotic resistance; tobramycin; tobramycin; tobramycin; Membrane Transport Proteins; carrier protein; piperacillin; loss of function mutation; Bacterial Proteins; bacterial protein; Polymyxin B; TRADE-OFF; COLLATERAL SENSITIVITY; aminoglycoside; bacterial membrane; colistin; fosfomycin; dequalinium; dequalinium; dequalinium; genetic background; microbial sensitivity test; fractional inhibitory concentration index; Antibiotic resistome; Drug Collateral Sensitivity; tobramycin resistance}, year = {2023}, eissn = {2041-1723} } @article{MTMT:33597267, title = {Identification of potent antimicrobial peptides via a machine-learning pipeline that mines the entire space of peptide sequences}, url = {https://m2.mtmt.hu/api/publication/33597267}, author = {Huang, J. and Xu, Y. and Xue, Y. and Huang, Y. and Li, X. and Chen, X. and Xu, Y. and Zhang, D. and Zhang, P. and Zhao, J. and Ji, J.}, doi = {10.1038/s41551-022-00991-2}, journal-iso = {NAT BIOMED ENG}, journal = {NATURE BIOMEDICAL ENGINEERING}, unique-id = {33597267}, issn = {2157-846X}, abstract = {Systematically identifying functional peptides is difficult owing to the vast combinatorial space of peptide sequences. Here we report a machine-learning pipeline that mines the hundreds of billions of sequences in the entire virtual library of peptides made of 6–9 amino acids to identify potent antimicrobial peptides. The pipeline consists of trainable machine-learning modules (for performing empirical selection, classification, ranking and regression tasks) assembled sequentially following a coarse-to-fine design principle to gradually narrow down the search space. The leading three antimicrobial hexapeptides identified by the pipeline showed strong activities against a wide range of clinical isolates of multidrug-resistant pathogens. In mice with bacterial pneumonia, aerosolized formulations of the identified peptides showed therapeutic efficacy comparable to penicillin, negligible toxicity and a low propensity to induce drug resistance. The machine-learning pipeline may accelerate the discovery of new functional peptides. © 2023, The Author(s), under exclusive licence to Springer Nature Limited.}, keywords = {PEPTIDES; AMINO-ACIDS; DESIGN PRINCIPLES; MICROORGANISMS; machine learning; MAMMALS; PIPELINES; Machine-learning; Digital libraries; Antimicrobial peptide; Virtual libraries; Peptide sequences; Functional peptides; Coarse to fine; Fine designs; Machine learning module}, year = {2023}, eissn = {2157-846X} } @mastersthesis{MTMT:34524601, title = {Impacts of Collateral Effects and Spatial Heterogeneity on the Evolution of Resistance in Enterococcus}, url = {https://m2.mtmt.hu/api/publication/34524601}, author = {Huynh, Anh}, doi = {10.7302/8398}, unique-id = {34524601}, year = {2023} } @article{MTMT:33773756, title = {The evolution of colistin resistance increases bacterial resistance to host antimicrobial peptides and virulence}, url = {https://m2.mtmt.hu/api/publication/33773756}, author = {Jangir, Pramod Kumar and Ogunlana, Lois and Szili, Petra and Czikkely, Márton Simon and Shaw, Liam P and Stevens, Emily J and Yang, Yu and Yang, Qiue and Wang, Yang and Pál, Csaba and Walsh, Timothy R and MacLean, Craig R}, doi = {10.7554/eLife.84395}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {12}, unique-id = {33773756}, issn = {2050-084X}, abstract = {Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that the evolution of resistance to therapeutic AMPs may generate cross-resistance to host AMPs, compromising a cornerstone of the innate immune response. We systematically tested this hypothesis using globally disseminated mobile colistin resistance (MCR) that has been selected by the use of colistin in agriculture and medicine. Here, we show that MCR provides a selective advantage to Escherichia coli in the presence of key AMPs from humans and agricultural animals by increasing AMP resistance. Moreover, MCR promotes bacterial growth in human serum and increases virulence in a Galleria mellonella infection model. Our study shows how the anthropogenic use of AMPs can drive the accidental evolution of resistance to the innate immune system of humans and animals. These findings have major implications for the design and use of therapeutic AMPs and suggest that MCR may be difficult to eradicate, even if colistin use is withdrawn.}, year = {2023}, eissn = {2050-084X}, orcid-numbers = {Jangir, Pramod Kumar/0000-0001-8330-0655} } @article{MTMT:33688217, title = {Time-lapse proteomics unveil constant high exposure of non-antibiotic drug induces synthetic susceptibility towards regular antibiotics}, url = {https://m2.mtmt.hu/api/publication/33688217}, author = {Khan, Z.A. and Warden, A.R. and Jiang, H. and Abdullah, A. and Ahmad, M. and Jiang, L. and Ding, X.}, doi = {10.1016/j.micres.2023.127320}, journal-iso = {MICROBIOL RES}, journal = {MICROBIOLOGICAL RESEARCH}, volume = {269}, unique-id = {33688217}, issn = {0944-5013}, abstract = {Antibiotic resistance is a significant threat to the human race, as regular consumption of antibiotics may lead to antibiotic-resistant bacterial strains. Non-antibiotic drugs also have an extensive impact on bacterial strains, where persistent uptake alters the survival mechanisms of bacteria that could lead to cross-resistance towards other antibiotics. Here, we use time-lapse proteomics shift assays to examine Gram-negative (E. coli. O157:H7 and P. aeruginosa) and Gram-positive (E. faecalis and S. aureus) strains of bacteria for short and continuous exposure to the non-antibiotic drug Hydroxychloroquine (HCQ). Proteomic transitions from wild type to HCQ-exposed strains revealed bacterial transitions and their survival adaptabilities, which were different across all strains. In addition to their structural differences, some shared pathways were enriched among Gram-negative and positive strains. We also validated the cross-resistance and sensitivity towards 24 regularly prescribed antibiotics, indicating that long-term exposure to non-antibiotic drugs may induce general proteomics alterations in the bacterial strains, promoting antibiotic resistance. We validated that HCQ exposure renders Gram-negative strains resistant to Β-lactam and susceptible to macrolides and folic acid. In contrast, Gram-positive strains become susceptible to Β-lactam and resistant to aminoglycosides. Exposure to non-antibiotic drugs causes resistance or susceptibility toward other antibiotics, providing clinicians a reason to overcome antibiotic resistance. © 2023 Elsevier GmbH}, keywords = {Humans; SURVIVAL; DRUG; BACTERIA; human; BETA-LACTAMS; ADAPTATION; Escherichia coli; Escherichia coli; Escherichia coli; Microbial Sensitivity Tests; bacterium; bacterium; antibiotics; antiinfective agent; Staphylococcus aureus; Staphylococcus aureus; Molecular Biology; proteomics; proteomics; proteomics; proteomics; proteomics; anti-bacterial agents; Drug Resistance, Bacterial; Antibiotic resistance; Antibiotic resistance; beta lactam; cross resistance; time-lapse imaging; CROSS-RESISTANCE; time lapse imaging; microbial sensitivity test; Bacterial resistance; Bacterial resistance; antibiotics resistance; antibiotics resistance; antibiotic susceptibilities; bacterial strains; Antibiotic drugs; Gram-positive strains; antibiotics susceptibility; Gram-negative strains; High exposures}, year = {2023}, eissn = {1618-0623} } @article{MTMT:34126799, title = {Recent advances in self-assembled cyclic peptide-based smart nanos-tructures}, url = {https://m2.mtmt.hu/api/publication/34126799}, author = {Kherwal, M. and Gupta, A. and Jacob, M. and Chandra, A. and Sahu, P.K. and Goel, V.K. and Kumar, V.}, doi = {10.24294/ace.v6i1.1989}, journal-iso = {ACE}, journal = {Applied Chemical Engineering}, volume = {6}, unique-id = {34126799}, abstract = {Peptide chemistry has emerged as one of the growing fields of research. Peptide chemistry has positively impacted various areas, including biochemistry, medicine, hormonal therapy, drug delivery, food and the cosmetic industry, materials science, and nanotechnology, via the development of ways to change and imitate the shape and function of peptide structures. The structural changes of peptides and the employment of innovative synthetic techniques have left an indelible mark on a number of scientific disciplines. Numerous nanostructures based on simple and complicated peptides have been constructed so far; however, cyclic peptides have attracted a great deal of interest from the scientific community due to their wide range of applications and distinctive properties. These properties include self-assembly, morphogenesis, and charge distribution, among others. In addition, nanostructured cyclic peptides offer increased and effective performance due to their high stability, prolonged plasma half-life, membrane permeability, and efficient transport, among other attributes. Recent work indicates the manufacture of nanostructured cyclic peptides by chemical means. In this review, a brief investigation of the morphology of cyclic peptides was conducted. In addition, the therapeutic potential of these nanostructured cyclic peptides and the prognosis for a variety of potential applications are also discussed. © 2023 by author(s).}, keywords = {PEPTIDES; NANOWIRES; Nanotubes; Drug delivery; Nanospheres; cyclic peptides; Therapeutic}, year = {2023}, eissn = {2578-2010}, pages = {104-116} } @article{MTMT:34136782, title = {The Effects of Preservatives on Antibiotic- and Preservative-Resistant Microbes and Nitrogen/Sulfur Cycle Associated Microbial Communities in Freshwater River Sediments}, url = {https://m2.mtmt.hu/api/publication/34136782}, author = {Liao, Chien-Sen and Cao, Xuan-Di and Lee, Wei-Chen and Yang, Chu-Wen}, doi = {10.3390/antibiotics12071082}, journal-iso = {ANTIBIOTICS-BASEL}, journal = {ANTIBIOTICS}, volume = {12}, unique-id = {34136782}, abstract = {The intensive use of benzoic acid (BA), 4-hydroxybenzoic acid (HB), and dehydroacetate (DHA) as additives and preservatives in cosmetics and foods causes emerging environmental pollutions. Anthropogenic releases of BA, HB and DHA are primarily emissions into water and soil. However, few studies investigate the effects of BA, HB and DHA on microbial communities in freshwater river sediments. The aim of this study is to reveal the effects of BA, HB and DHA on microbial communities in freshwater river sediments. Tetracycline-, sulfamethoxazole- and preservative-resistant microbes were increased in the river sediments treated with BA, HB and DHA. The relative abundances of methanogen- and xenobiotic-degradation-associated microbial communities were also increased in the BA-, HB- and DHA-treated sediments. The relative abundance of four nitrogen cycle associated microbial groups (anammox, nitrogen fixation, denitrification, and dissimilatory nitrate reduction) were increased after the eighth week in the BA-, HB- and DHA-treated sediments. For the sulfur cycle, the relative abundance of thiosulfate oxidation associated microbial communities were increased after the eighth week in the BA-, HB- and DHA-treated sediments. Results of this study provide insight into the effects of BA, HB and DHA on antibiotic resistance, nitrogen cycle, sulfur cycle, drug resistance and methane production in freshwater aquatic environments.}, year = {2023}, eissn = {2079-6382} } @article{MTMT:34312619, title = {An additive-free multifunctional β-glucan-peptide hydrogel participates in the whole process of bacterial-infected wound healing}, url = {https://m2.mtmt.hu/api/publication/34312619}, author = {Li, Li and Wang, Yinglu and Huang, Zhengjun and Xu, Zuxian and Cao, Ruipin and Li, Jiaxin and Wu, Biyi and Lu, Jian Ren and Zhu, Hu}, doi = {10.1016/j.jconrel.2023.09.010}, journal-iso = {J CONTROL RELEASE}, journal = {JOURNAL OF CONTROLLED RELEASE}, volume = {362}, unique-id = {34312619}, issn = {0168-3659}, abstract = {Bacterial infections and excessive inflammation can impede the healing of wounds. Hydrogels have emerged as a promising approach for dressing bacterial-infected injuries. However, some antibacterial hydrogels are complex, costly, and even require assistance with other instruments such as light, making them unsuitable for routine outdoor injuries. Here, we developed an in-situ generating hydrogel via hybridizing oxidized beta-D-glucan with antimicrobial peptide C(8)G(2) through the Schiff base reaction. This hydrogel is easily accessible and actively contributes to the whole healing process of bacterial-infected wounds, demonstrating remarkable antibacterial activity and biological compatibility. The pH-sensitive reversible imine bond enables the hydrogel to self-heal and sustainably release the antibacterial peptide, thereby improving its bioavailability and reducing toxicity. Meanwhile, the immunoregulating beta-D-glucan inhibits the release of inflammatory factors while promoting the release of anti-inflammatory factors. In methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin wound models, the hybrid hydrogel showed superior antibacterial and anti-inflammatory activity, enhanced the M2 macrophage polarization, expedited wound closure, and regenerated epidermis tissue. These features make this hydrogel an appealing wound dressing for treating multi-drug-resistant bacteria-infected wounds.}, keywords = {ANTIBACTERIAL; Wound healing; Anti-inflammation; Beta-glucan; Injectable hydrogel}, year = {2023}, eissn = {1873-4995}, pages = {577-590} } @article{MTMT:33781796, title = {Collateral sensitivity profiling in drug-resistant Escherichia coli identifies natural products suppressing cephalosporin resistance}, url = {https://m2.mtmt.hu/api/publication/33781796}, author = {Liu, D.Y. and Phillips, L. and Wilson, D.M. and Fulton, K.M. and Twine, S.M. and Wong, A. and Linington, R.G.}, doi = {10.1038/s41467-023-37624-4}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {14}, unique-id = {33781796}, issn = {2041-1723}, abstract = {The rapid emergence of antimicrobial resistance presents serious health challenges to the management of infectious diseases, a problem that is further exacerbated by slowing rates of antimicrobial drug discovery in recent years. The phenomenon of collateral sensitivity (CS), whereby resistance to one drug is accompanied by increased sensitivity to another, provides new opportunities to address both these challenges. Here, we present a high-throughput screening platform termed Collateral Sensitivity Profiling (CSP) to map the difference in bioactivity of large chemical libraries across 29 drug-resistant strains of E. coli. CSP screening of 80 commercial antimicrobials demonstrated multiple CS interactions. Further screening of a 6195-member natural product library revealed extensive CS relationships in nature. In particular, we report the isolation of known and new analogues of borrelidin A with potent CS activities against cephalosporin-resistant strains. Co-dosing ceftazidime with borrelidin A slows broader cephalosporin resistance with no recognizable resistance to borrelidin A itself. © 2023, The Author(s).}, keywords = {Humans; human; Escherichia coli; Escherichia coli; Microbial Sensitivity Tests; antiinfective agent; anti-bacterial agents; Anti-Infective Agents; Escherichia coli Infections; Biological Products; biological product; Escherichia coli infection; borrelidin; microbial sensitivity test; cephalosporin resistance; cephalosporin resistance; Drug Collateral Sensitivity}, year = {2023}, eissn = {2041-1723} } @article{MTMT:34136781, title = {Treatment of Superbug Infection through a Membrane-Disruption and Immune-Regulation Cascade Effect Based on Supramolecular Peptide Hydrogels}, url = {https://m2.mtmt.hu/api/publication/34136781}, author = {Liu, Yanchen and Gong, Haoning and Wang, Zhiwei and Yuan, Chengqian and Lu, Jianren and Yan, Xuehai}, doi = {10.1002/adfm.202305726}, journal-iso = {ADV FUNCT MATER}, journal = {ADVANCED FUNCTIONAL MATERIALS}, unique-id = {34136781}, issn = {1616-301X}, year = {2023}, eissn = {1616-3028} } @article{MTMT:33759567, title = {Host-Defense-Peptide-Mimicking β-Peptide Polymer Acting as a Dual-Modal Antibacterial Agent by Interfering Quorum Sensing and Killing Individual Bacteria Simultaneously}, url = {https://m2.mtmt.hu/api/publication/33759567}, author = {Li, W. and Xiao, X. and Qi, Y. and Lin, X. and Hu, H. and Shi, M. and Zhou, M. and Jiang, W. and Liu, L. and Chen, K. and Wang, K. and Liu, R. and Zhou, M.}, doi = {10.34133/research.0051}, journal-iso = {RESEARCH-CHINA}, journal = {RESEARCH}, volume = {6}, unique-id = {33759567}, issn = {2096-5168}, abstract = {Host defense peptides (HDPs) are one of the potentially promising agents for infection diseases due to their broad spectrum and low resistance rate, but their clinical applications are limited by proteolytic instability, high-cost, and complicated synthesis process. Here, we report a host-defense-peptide-mimicking β-peptide polymer that resists proteolysis to have enhanced the activity under physiological conditions, excellent antimicrobial efficiency even at high density of bacteria, and low cost for preparation. The β-peptide polymer demonstrated quorum sensing (QS) interference and bactericidal effect against both bacterial communities and individual bacterium to simultaneously block bacterial communication and disrupt bacterial membranes. The hierarchical QS network was suppressed, and main QS signaling systems showed considerably down-regulated gene expression, resulting in excellent biofilm eradication and virulence reduction effects. The dual-modal antibacterial ability possessed excellent therapeutic effects in Pseudomonas aeruginosa pneumonia, which could inhibit biofilm formation and exhibit better antibacterial and anti-inflammatory efficiency than clinically used antibiotics, levofloxacin. Furthermore, the β-peptide polymer also showed excellent therapeutic effect Escherichia coli pyogenic liver abscess. Together, we believed that the β-peptide polymer had a feasible clinical potential to treat bacterial infection diseases. © 2023 Wanlin Li et al.}, keywords = {PEPTIDES; EFFICIENCY; Escherichia coli; Gene Expression; antibiotics; ANTIBACTERIALS; BIOFILMS; clinical application; Hierarchical systems; Host defense; Network security; quorum-sensing; Therapeutic effects; High costs; broad spectrum; resistance rate; Low resistance; Infections disease}, year = {2023}, eissn = {2639-5274} } @article{MTMT:34025035, title = {Construction of palladium porphyrins and triptycene photo-activated nanomaterial for enhanced colorimetric detection and inactivation of bacteria}, url = {https://m2.mtmt.hu/api/publication/34025035}, author = {Li, Y. and Wang, Q. and Qu, X. and Tian, J. and Zhang, X.}, doi = {10.1016/j.jcis.2023.05.190}, journal-iso = {J COLLOID INTERF SCI}, journal = {JOURNAL OF COLLOID AND INTERFACE SCIENCE}, volume = {648}, unique-id = {34025035}, issn = {0021-9797}, abstract = {In the face of increasing bacterial resistance, design of high-performing and dual-functional nanomaterials to satisfy the requirements for both detecting and eradicating bacteria is of immense importance, but still remains a great challenge. Herein, a hierarchically three-dimensional (3D) porous organic frameworks (PdPPOPHBTT) was rationally designed and fabricated for the first time to realize ideal simultaneous detection and eradication of bacteria. PdPPOPHBTT covalently integrated palladium 5,10,15,20-tetrakis-(4′-bromophenyl) porphyrin (PdTBrPP, an excellent photosensitizer) with 2,3,6,7,12,13-hexabromotriptycene (HBTT, a 3D building module). The resulting material had outstanding NIR absorption, narrow bad gap and robust singlet oxygen (1O2) production capacity, which is responsible for the sensitive detection and effective removal of bacteria. We successfully realized the colorimetric detection of S. aureus and the efficient removal of S. aureus and E. coli. The first-principles calculations found at the highly activated 1O2 derived from the 3D conjugated periodic structures and ample palladium adsorption site in PdPPOPHBTT. The bacterial infection wound model revealed that PdPPOPHBTT possesses good disinfection ability and negligible side effect to normal tissue in vivo. This finding provides an innovative strategy for designing individual porous organic polymer (POPs) with multi-function and also broaden the applications of POPs as powerful nonantibiotic type of antimicrobials. © 2023}, keywords = {DNA; PALLADIUM; nanostructured materials; antibacterial activity; Porphyrins; colorimetry; image enhancement; PHOTOSENSITIZERS; photosensitizer; Anti-bacterial activity; Colorimetric detection; S. aureus; Bacterial resistance; porous organic polymers; porous organic polymers; Photo-activated; Photosensitiser; triptycene; triptycenes; Functional Nano materials; palladium porphyrins; palladium porphyrins}, year = {2023}, eissn = {1095-7103}, pages = {220-230} } @article{MTMT:34617070, title = {Molecular de-extinction of ancient antimicrobial peptides enabled by machine learning}, url = {https://m2.mtmt.hu/api/publication/34617070}, author = {Maasch, Jacqueline R. M. A. and Torres, Marcelo D. T. and Melo, Marcelo C. R. and de la Fuente-Nunez, Cesar}, doi = {10.1016/j.chom.2023.07.001}, journal-iso = {CELL HOST MICROBE}, journal = {CELL HOST & MICROBE}, volume = {31}, unique-id = {34617070}, issn = {1931-3128}, abstract = {Molecular de-extinction could offer avenues for drug discovery by reintroducing bioactive molecules that are no longer encoded by extant organisms. To prospect for antimicrobial peptides encrypted within extinct and extant human proteins, we introduce the panCleave random forest model for proteome-wide cleavage site prediction. Our model outperformed multiple protease-specific cleavage site classifiers for three modern human caspases, despite its pan-protease design. Antimicrobial activity was observed in vitro for modern and archaic protein fragments identified with panCleave. Lead peptides showed resistance to proteolysis and exhibited variable membrane permeabilization. Additionally, representative modern and archaic protein fragments showed anti-infective efficacy against A. baumannii in both a skin abscess infection model and a pre clinical murine thigh infection model. These results suggest that machine-learning-based encrypted peptide prospection can identify stable, nontoxic peptide antibiotics. Moreover, we establish molecular de-extinction through paleoproteome mining as a framework for antibacterial drug discovery.}, year = {2023}, eissn = {1934-6069} } @article{MTMT:34025036, title = {New electrochemical reactor design for emergent pollutants removal by electrochemical oxidation}, url = {https://m2.mtmt.hu/api/publication/34025036}, author = {Montenegro-Ayo, R. and Pérez, T. and Lanza, M.R.V. and Brillas, E. and Garcia-Segura, S. and dos, Santos A.J.}, doi = {10.1016/j.electacta.2023.142551}, journal-iso = {ELECTROCHIM ACTA}, journal = {ELECTROCHIMICA ACTA}, volume = {458}, unique-id = {34025036}, issn = {0013-4686}, abstract = {This paper presents the theoretical and experimental confirmation of the performance of a novel pre-pilot reactor design implementing a boron-doped diamond (BDD) anode to destroy emerging pollutants by electrochemical oxidation. Turbulent flow simulation and secondary current distribution modeling with a COMSOL Multiphysics software were used to assess the engineering capabilities of the reactor along with the oxidant BDD(·OH) electrogeneration at the anode. The antibiotic ciprofloxacin (CIP) was chosen as model molecule to assess the oxidation power achieved with the pre-pilot batch plant. In sulfate medium where BDD(·OH) was the main oxidant, faster degradation was determined by increasing current density, CIP content, and pH. The effect of pH was explained by the transformation of the cationic form of CIP in acidic medium into its more easily oxidizable anionic form in alkaline medium. In chloride medium, CIP was more rapidly removed by the faster attack of the generated active chlorine. The degradation was decelerated in carbonate medium by its scavenging effect and in the presence of humic acid by its competitive oxidation with BDD(·OH). The antibiotic abatement also dropped down in tap water and synthetic urine. An almost total mineralization was achieved with a constant energy cost per unit COD mass of 0.6 ± 0.1 kWh (g COD)−1. The initial N of CIP was pre-eminently converted into nitrate, alongside nitrite and ammonia to lesser extent. Recalcitrant acetic, oxalic, and formic acids were detected as final carboxylic acids. © 2023 Elsevier Ltd}, keywords = {SULFUR COMPOUNDS; AMMONIA; computer software; HYDROXYL RADICALS; antibiotics; ciprofloxacin; ciprofloxacin; boron; Hydroxyl Radical; chlorine; Chemical oxygen demand; Chlorine compounds; oxalic acid; Oxidants; alkalinity; wastewater treatment; wastewater treatment; ELECTROCHEMICAL OXIDATION; Boolean functions; Multi-physics; ANODES; Reactor designs; COMSOL Multiphysics; Multiphysics; DISTRIBUTION MODELS; Active chlorine; Active chlorine; Boron doped diamond; Electric current distribution measurement; Secondary current distribution model; Secondary current distribution model; COMSOL multiphysic; Secondary current distributions}, year = {2023}, eissn = {1873-3859} } @article{MTMT:33922528, title = {In Vitro Investigation of the Antibacterial Activity of Salamander Skin Peptides}, url = {https://m2.mtmt.hu/api/publication/33922528}, author = {Pereira, Kenzie E. and Deslouches, Jakobi T. and Deslouches, Berthony and Woodley, Sarah K.}, doi = {10.1007/s00284-023-03320-1}, journal-iso = {CURR MICROBIOL}, journal = {CURRENT MICROBIOLOGY}, volume = {80}, unique-id = {33922528}, issn = {0343-8651}, abstract = {Given the current and future costs of antibiotic-resistant bacteria to human health and economic productivity, there is an urgent need to develop new antimicrobial compounds. Antimicrobial peptides are a promising alternative to conventional antibiotics and other antimicrobials. Amphibian skin is a rich source of bioactive compounds, but the antibacterial properties of salamander skin peptides have been neglected. Here, we examined the in vitro ability of skin peptides from 9 species of salamander representing 6 salamander families to inhibit the growth of ESKAPE pathogens, which are bacteria that have developed resistance to conventional antibiotics. We also examined whether the skin peptides caused lysis of human red blood cells. Skin peptides from Amphiuma tridactylum had the greatest antimicrobial properties, completely inhibiting the growth of all bacterial strains except for Enterococcus faecium. Likewise, skin peptides from Cryptobranchus alleganiensis completely inhibited the growth of several of the bacterial strains. In contrast, skin peptide mixtures from Ambystoma maculatum, Desmognathus fuscus, Eurycea bislineata, E. longicauda, Necturus beyeri, N. maculosus, and Siren intermedia did not completely inhibit bacterial growth even at the highest concentrations. Finally, none of the skin peptide mixtures caused lysis of human red blood cells. Together, we demonstrate that salamander skin produces peptides with potent antibacterial properties. It remains to elucidate the peptide sequences and their antibacterial mechanisms.}, year = {2023}, eissn = {1432-0991} } @article{MTMT:34523033, title = {Bioengineering the Antimicrobial Activity of Yeast by Recombinant Thanatin Production}, url = {https://m2.mtmt.hu/api/publication/34523033}, author = {Pipiya, S.O. and Kudzhaev, A.M. and Mirzoeva, N.Z. and Mokrushina, Y.A. and Ziganshin, R.H. and Komlev, A.S. and Petrova, P.E. and Smirnov, I.V. and Gabibov, A.G. and Shamova, O.V. and Terekhov, S.S.}, doi = {10.3390/antibiotics12121719}, journal-iso = {ANTIBIOTICS-BASEL}, journal = {ANTIBIOTICS}, volume = {12}, unique-id = {34523033}, abstract = {The global spread of antibiotic resistance marks the end of the era of conventional antibiotics. Mankind desires new molecular tools to fight pathogenic bacteria. In this regard, the development of new antimicrobials based on antimicrobial peptides (AMPs) is again of particular interest. AMPs have various mechanisms of action on bacterial cells. Moreover, AMPs have been reported to be efficient in preclinical studies, demonstrating a low level of resistance formation. Thanatin is a small, beta-hairpin antimicrobial peptide with a bacterial-specific mode of action, predetermining its low cytotoxicity toward eukaryotic cells. This makes thanatin an exceptional candidate for new antibiotic development. Here, a microorganism was bioengineered to produce an antimicrobial agent, providing novel opportunities in antibiotic research through the directed creation of biocontrol agents. The constitutive heterologous production of recombinant thanatin (rThan) in the yeast Pichia pastoris endows the latter with antibacterial properties. Optimized expression and purification conditions enable a high production level, yielding up to 20 mg/L of rThan from the culture medium. rThan shows a wide spectrum of activity against pathogenic bacteria, similarly to its chemically synthesized analogue. The designed approach provides new avenues for AMP engineering and creating live biocontrol agents to fight antibiotic resistance. © 2023 by the authors.}, keywords = {PEPTIDE; ARTICLE; YEAST; CYTOTOXICITY; high performance liquid chromatography; genetic recombination; Escherichia coli; Mass spectrometry; unclassified drug; minimum inhibitory concentration; Circular Dichroism; ciprofloxacin; protein purification; Staphylococcus aureus; PEPTIDE SYNTHESIS; ANTIMICROBIAL ACTIVITY; ANTIMICROBIAL PEPTIDES; Antifungal activity; antibacterial activity; Pseudomonas aeruginosa; Antibiotic resistance; Antibiotic resistance; plasmid; expression vector; Liquid chromatography-Mass spectrometry; electrospray; colony forming unit; Electroporation; MTT assay; polypeptide antibiotic agent; Bioengineering; Acinetobacter baumannii; CRISPR Cas system; Komagataella pastoris; Thanatin; Thanatin; recombinant antibiotics; yeast biocontrol agents}, year = {2023}, eissn = {2079-6382} } @article{MTMT:33759568, title = {The Synthetic Antimicrobial Peptide Derived From Melittin Displays Low Toxicity and Anti-infectious Properties}, url = {https://m2.mtmt.hu/api/publication/33759568}, author = {Rad, P.M. and Rahbarnia, L. and Safary, A. and ShadiDizaji, A. and Maani, Z.}, doi = {10.1007/s12602-023-10066-6}, journal-iso = {PROBIOTICS ANTIMICROB PROTEINS}, journal = {PROBIOTICS AND ANTIMICROBIAL PROTEINS}, unique-id = {33759568}, issn = {1867-1306}, abstract = {The low stability and nonspecific toxicity are the main limiting factors for the clinical applications of melittin (MLT). This study aimed to design and synthesize new analogs of MLT to increase stability, reduce toxicity, and retain their antimicrobial properties against bacterial pathogens. At first, peptide analogs were designed computationally by inducing single mutations in MLT peptides and evaluating their physicochemical properties. The stability of the analogs with the highest scores was determined by Gromacs software. In vitro assays were performed to examine the antimicrobial activity and toxicity of the selected analogs. Two peptide analogs, M1 and M2, were selected based on the SVM score in cell PPD. The M1 analog was created by replacing alanine with leucine on the 15th. The M2 analog was designed by substituting alanine with leucine and isoleucine with arginine at the 15th and 17th positions. According to the Gromacs results, the M2 peptide indicated more stability. RMSD and RMSF results showed no undesirable fluctuations during the 200 ns MD simulation. The MIC and MBC values for the M1 peptide were calculated in a range of 8–128 μg/ml, while the M2 peptide limited the bacterial growth to 32–128 μg/mL. Both peptides indicated less toxicity than natural MLT, based on MTT assay results. The hemolytic activity of the M1 analog was more than M2 at 16 μg/mL concentration. M1 peptide displayed the highest selectivity index against S. aureus and A. baumannii, which were approximately 5.27-fold improvements compared to MLT. In conclusion, we introduced two analogs of MLT with low toxicity, low hemolytic activity, and higher stability, along with retaining antimicrobial properties against gram-negative and positive bacteria. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.}, keywords = {antibacterial activity; MD simulation; Peptide analog}, year = {2023}, eissn = {1867-1314} } @article{MTMT:33995750, title = {Translating eco-evolutionary biology into therapy to tackle antibiotic resistance}, url = {https://m2.mtmt.hu/api/publication/33995750}, author = {Sanz-Garcia, Fernando and Gil-Gil, Teresa and Laborda, Pablo and Blanco, Paula and Ochoa-Sanchez, Luz-Edith and Baquero, Fernando and Martinez, Jose Luis and Hernando-Amado, Sara}, doi = {10.1038/s41579-023-00902-5}, journal-iso = {NAT REV MICROBIOL}, journal = {NATURE REVIEWS MICROBIOLOGY}, unique-id = {33995750}, issn = {1740-1526}, abstract = {In this Review, Martinez, Hernando-Amado and colleagues explore how eco-evolutionary-based approaches can aid in the design of successful antibiotic therapies, including the exploitation of evolutionary trade-offs, targeting bacterial metabolism and studying the ancestral functions of antibiotic resistance determinants.Antibiotic resistance is currently one of the most important public health problems. The golden age of antibiotic discovery ended decades ago, and new approaches are urgently needed. Therefore, preserving the efficacy of the antibiotics currently in use and developing compounds and strategies that specifically target antibiotic-resistant pathogens is critical. The identification of robust trends of antibiotic resistance evolution and of its associated trade-offs, such as collateral sensitivity or fitness costs, is invaluable for the design of rational evolution-based, ecology-based treatment approaches. In this Review, we discuss these evolutionary trade-offs and how such knowledge can aid in informing combination or alternating antibiotic therapies against bacterial infections. In addition, we discuss how targeting bacterial metabolism can enhance drug activity and impair antibiotic resistance evolution. Finally, we explore how an improved understanding of the original physiological function of antibiotic resistance determinants, which have evolved to reach clinical resistance after a process of historical contingency, may help to tackle antibiotic resistance.}, year = {2023}, eissn = {1740-1534}, orcid-numbers = {Laborda, Pablo/0000-0001-8281-7900; Baquero, Fernando/0000-0002-7930-3033} } @article{MTMT:34480007, title = {Exploring the arsenal of antimicrobial peptides: Mechanisms, diversity, and applications}, url = {https://m2.mtmt.hu/api/publication/34480007}, author = {Savitskaya, A. and Masso-Silva, J. and Haddaoui, I. and Enany, S.}, doi = {10.1016/j.biochi.2023.07.016}, journal-iso = {BIOCHIMIE}, journal = {BIOCHIMIE}, volume = {214}, unique-id = {34480007}, issn = {0300-9084}, year = {2023}, eissn = {1638-6183}, pages = {216-227} } @article{MTMT:34524545, title = {Photopolymerized keratin-PGLa hydrogels for antibiotic resistance reversal and enhancement of infectious wound healing}, url = {https://m2.mtmt.hu/api/publication/34524545}, author = {Sun, Changfa and Liu, Wenjie and Wang, Lili and Meng, Run and Deng, Jia and Qing, Rui and Wang, Bochu and Hao, Shilei}, doi = {10.1016/j.mtbio.2023.100807}, journal-iso = {MATER TODAY BIO}, journal = {MATERIALS TODAY BIO}, volume = {23}, unique-id = {34524545}, year = {2023}, eissn = {2590-0064}, pages = {100807}, orcid-numbers = {Sun, Changfa/0000-0001-7773-8343; Meng, Run/0000-0002-0867-0733; Qing, Rui/0000-0002-7952-2295; Hao, Shilei/0000-0003-1205-3102} } @article{MTMT:34524612, title = {A new class of antimicrobial therapeutics targeting the envelope stress response of Gram-negative bacteria: abridged secondary publication}, url = {https://m2.mtmt.hu/api/publication/34524612}, author = {Tang, SW and Kwok, SH and Li, X and Tang, KH and Kubi, JA and Brah, AS and Yeung, K and Dong, M and Lam, YW}, journal-iso = {HONG KONG MED J}, journal = {HONG KONG MEDICAL JOURNAL}, volume = {29:}, unique-id = {34524612}, issn = {1024-2708}, year = {2023}, eissn = {1024-2708}, pages = {S39-S44} } @article{MTMT:33759560, title = {The evolution of antibiotic resistance is associated with collateral drug phenotypes in Mycobacterium tuberculosis}, url = {https://m2.mtmt.hu/api/publication/33759560}, author = {Waller, N.J.E. and Cheung, C.-Y. and Cook, G.M. and McNeil, M.B.}, doi = {10.1038/s41467-023-37184-7}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {14}, unique-id = {33759560}, issn = {2041-1723}, abstract = {The increasing incidence of drug resistance in Mycobacterium tuberculosis has diminished the efficacy of almost all available antibiotics, complicating efforts to combat the spread of this global health burden. Alongside the development of new drugs, optimised drug combinations are needed to improve treatment success and prevent the further spread of antibiotic resistance. Typically, antibiotic resistance leads to reduced sensitivity, yet in some cases the evolution of drug resistance can lead to enhanced sensitivity to unrelated drugs. This phenomenon of collateral sensitivity is largely unexplored in M. tuberculosis but has the potential to identify alternative therapeutic strategies to combat drug-resistant strains that are unresponsive to current treatments. Here, by using drug susceptibility profiling, genomics and evolutionary studies we provide evidence for the existence of collateral drug sensitivities in an isogenic collection M. tuberculosis drug-resistant strains. Furthermore, in proof-of-concept studies, we demonstrate how collateral drug phenotypes can be exploited to select against and prevent the emergence of drug-resistant strains. This study highlights that the evolution of drug resistance in M. tuberculosis leads to collateral drug responses that can be exploited to design improved drug regimens. © 2023, The Author(s).}, keywords = {Humans; PHENOTYPE; PHENOTYPE; PHENOTYPE; GENETICS; EVOLUTION; GENOMICS; human; microbiology; Drug Resistance; tuberculosis; tuberculosis; tuberculosis; emergence; Microbial Sensitivity Tests; bacterium; multidrug resistance; Mycobacterium tuberculosis; Mycobacterium tuberculosis; Antitubercular Agents; tuberculostatic agent; Antibiotic resistance; Drug Resistance, Multiple, Bacterial; multidrug resistant tuberculosis; microbial sensitivity test; Tuberculosis, Multidrug-Resistant}, year = {2023}, eissn = {2041-1723} } @article{MTMT:34126800, title = {AMP-EBiLSTM: employing novel deep learning strategies for the accurate prediction of antimicrobial peptides}, url = {https://m2.mtmt.hu/api/publication/34126800}, author = {Wang, Y. and Wang, L. and Li, C. and Pei, Y. and Liu, X. and Tian, Y.}, doi = {10.3389/fgene.2023.1232117}, journal-iso = {FRONT GENET}, journal = {FRONTIERS IN GENETICS}, volume = {14}, unique-id = {34126800}, abstract = {Antimicrobial peptides are present ubiquitously in intra- and extra-biological environments and display considerable antibacterial and antifungal activities. Clinically, it has shown good antibacterial effect in the treatment of diabetic foot and its complications. However, the discovery and screening of antimicrobial peptides primarily rely on wet lab experiments, which are inefficient. This study endeavors to create a precise and efficient method of predicting antimicrobial peptides by incorporating novel machine learning technologies. We proposed a deep learning strategy named AMP-EBiLSTM to accurately predict them, and compared its performance with ensemble learning and baseline models. We utilized Binary Profile Feature (BPF) and Pseudo Amino Acid Composition (PSEAAC) for effective local sequence capture and amino acid information extraction, respectively, in deep learning and ensemble learning. Each model was cross-validated and externally tested independently. The results demonstrate that the Enhanced Bi-directional Long Short-Term Memory (EBiLSTM) deep learning model outperformed others with an accuracy of 92.39% and AUC value of 0.9771 on the test set. On the other hand, the ensemble learning models demonstrated cost-effectiveness in terms of training time on a T4 server equipped with 16 GB of GPU memory and 8 vCPUs, with training durations varying from 0 to 30 s. Therefore, the strategy we propose is expected to predict antimicrobial peptides more accurately in the future. Copyright © 2023 Wang, Wang, Li, Pei, Liu and Tian.}, keywords = {ARTICLE; PREDICTION; human; ALGORITHM; amino acid sequence; controlled study; Reliability; machine learning; reproducibility; hydrophilicity; FREQUENCY; sigmoid; ANTIMICROBIAL PEPTIDES; Antifungal activity; antibacterial activity; Hydrophobicity; histogram; bioinformatics; diagnostic test accuracy study; polypeptide antibiotic agent; Isoelectric point; short term memory; Data accuracy; support vector machine; Ensemble learning; Convolutional neural network; Deep learning; Deep learning; Diabetic Foot; Diabetic Foot; Recurrent neural network; long short term memory network; accurate screening}, year = {2023}, eissn = {1664-8021} } @article{MTMT:34124743, title = {The pharmacokinetic–pharmacodynamic modelling framework as a tool to predict drug resistance evolution}, url = {https://m2.mtmt.hu/api/publication/34124743}, author = {Witzany, Christopher and Rolff, Jens and Regoes, Roland R. and Igler, Claudia}, doi = {10.1099/mic.0.001368}, journal-iso = {MICROBIOL-SGM}, journal = {MICROBIOLOGY-SGM}, volume = {169}, unique-id = {34124743}, issn = {1350-0872}, abstract = {Pharmacokinetic–pharmacodynamic (PKPD) models, which describe how drug concentrations change over time and how that affects pathogen growth, have proven highly valuable in designing optimal drug treatments aimed at bacterial eradication. However, the fast rise of antimicrobial resistance calls for increased focus on an additional treatment optimization criterion: avoidance of resistance evolution. We demonstrate here how coupling PKPD and population genetics models can be used to determine treatment regimens that minimize the potential for antimicrobial resistance evolution. Importantly, the resulting modelling framework enables the assessment of resistance evolution in response to dynamic selection pressures, including changes in antimicrobial concentration and the emergence of adaptive phenotypes. Using antibiotics and antimicrobial peptides as an example, we discuss the empirical evidence and intuition behind individual model parameters. We further suggest several extensions of this framework that allow a more comprehensive and realistic prediction of bacterial escape from antimicrobials through various phenotypic and genetic mechanisms.}, year = {2023}, eissn = {1465-2080}, pages = {001368}, orcid-numbers = {Witzany, Christopher/0000-0002-7128-6419; Rolff, Jens/0000-0002-1529-5409; Regoes, Roland R./0000-0001-8319-5293; Igler, Claudia/0000-0001-7777-546X} } @article{MTMT:33688218, title = {Discovery and Mechanism of Action of a Novel Antimicrobial Peptide from an Earthworm}, url = {https://m2.mtmt.hu/api/publication/33688218}, author = {Wu, Y. and Deng, S. and Wang, X. and Thunders, M. and Qiu, J. and Li, Y.}, doi = {10.1128/spectrum.03206-22}, journal-iso = {MICROBIOL SPEC}, journal = {MICROBIOLOGY SPECTRUM}, volume = {11}, unique-id = {33688218}, issn = {2165-0497}, abstract = {The robust innate immune system of the earthworm provides a potential source of natural antimicrobial peptides (AMPs). However, the cost and high rediscovery rate of direct separation and purification limits their discovery. Genome sequencing of numerous earthworm species facilitates the discovery of new antimicrobial peptides. Through predicting potential antimicrobial peptides in the open reading frames of the Eisenia andrei genome and sequence optimization, a novel antimicrobial peptide, named EWAMP-R (RIWWSGGWRRWRW), was identified. EWAMP-R demonstrated good activity against various bacteria, including drug-resistant strains. The antibacterial mechanisms of EWAMP-R were explored through molecular simulation and wet-laboratory experiments. These experiments demonstrated that the bacterial membrane may be one of the targets of EWAMP-R but that there may be different interactions with Gram-negative and Gram-positive bacterial membranes. EWAMP-R can disrupt bacterial membrane integrity; however, at low concentrations, it appears that EWAMP-R may get through the membrane of Escherichia coli instead of damaging it directly, implying the existence of a secondary response. Gene expression studies identified that in E. coli, only the apoptosislike cell death (ALD) pathway was activated, while in Staphylococcus aureus, the MazEF pathway was also upregulated, limiting the influence of the ALD pathway. The different antimicrobial actions against Gram-positive and -negative bacteria can provide important information on the structure-activity relationship of AMPs and facilitate AMP design with higher specificity. This study identified a new source of antibacterial agents that has the potential to address the increasingly serious issue of antibiotic resistance. IMPORTANCE Drug-resistant bacteria are a great threat to public health and drive the search for new antibacterial agents. The living environment of earthworms necessitates a strong immune system, and therefore, they are potentially a rich resource of novel antibiotics. A novel AMP, EWAMP-R, with high antibacterial activity was found through in silico analysis of the Eisenia andrei genome. Molecular analysis investigating the interactions between EWAMP-R and the cell membrane demonstrated the importance of tryptophan and arginine residues to EWAMP-R activity. Additionally, the different secondary responses found between E. coli and S. aureus were in accordance with a common phenomenon where some antibacterial agents only target specific species of bacteria. These results provided useful molecular information to support further AMP research and design. Our study expands the sources of antimicrobial peptides and also helps to explain the adaptability of earthworms to their environment. © 2023 Wu et al.}, keywords = {Animals; GENETICS; OLIGOCHAETA; OLIGOCHAETA; BACTERIA; animal; Chemistry; Escherichia coli; Escherichia coli; Microbial Sensitivity Tests; bacterium; antiinfective agent; Staphylococcus aureus; Staphylococcus aureus; ANTIMICROBIAL PEPTIDES; antibacterial activity; anti-bacterial agents; MOLECULAR SIMULATION; earthworm; polypeptide antibiotic agent; bacterial membrane; Antimicrobial Cationic Peptides; Antimicrobial peptide; antimicrobial cationic peptide; microbial sensitivity test}, year = {2023}, eissn = {2165-0497} } @article{MTMT:34075931, title = {Novel antimicrobial peptide DvAMP serves as a promising antifungal agent against Cryptococcus neoformans}, url = {https://m2.mtmt.hu/api/publication/34075931}, author = {Yang, Longbing and Tian, Zhuqing and Zhao, Wenjing and Zhang, Jin and Tian, Chunren and Zhou, Luoxiong and Jiao, Zhenlong and Peng, Jian and Guo, Guo}, doi = {10.1016/j.bioorg.2023.106679}, journal-iso = {BIOORG CHEM}, journal = {BIOORGANIC CHEMISTRY}, volume = {138}, unique-id = {34075931}, issn = {0045-2068}, year = {2023}, eissn = {1090-2120} } @article{MTMT:33759561, title = {Antimicrobial Zeolitic Imidazolate Frameworks with Dual Mechanisms of Action}, url = {https://m2.mtmt.hu/api/publication/33759561}, author = {Yan, Y. and Li, Y. and Li, H. and Ma, X. and Tang, Y. and Yi, K. and Lin, X. and Li, J. and Liu, Z.}, doi = {10.1021/acsinfecdis.2c00496}, journal-iso = {ACS INFECT DIS}, journal = {ACS INFECTIOUS DISEASES}, volume = {9}, unique-id = {33759561}, issn = {2373-8227}, abstract = {The horizontal transfer of drug-resistant genes and the formation of biofilm barriers have threatened the therapeutic efficacy of conventional antibiotic drugs. Development of non-antibiotic agents with high delivery efficiency through bacterial biofilms is urgently required. A pyrithione (PT)-loading zeolitic imidazolate framework (ZIF-8@PT) is synthesized to destroy biofilms and improve the sensitivity of bacteria to PT. ZIF-8@PT can target and destroy the biofilm as well as the cell membrane, promoting the intracellular delivery of PT and possibly its interaction with SmpB, a protein that could regulate the drug resistance of bacteria. ZIF-8@PT effectively suppresses abdominal infections induced by multiresistant Aeromonas veronii C4 in rodent models without systemic toxicity. ZIF-8@PT promises wide applications in treating infections caused by multidrug-resistant bacteria through a dual mechanism of action. © 2023 American Chemical Society.}, keywords = {PH; ARTICLE; MOUSE; controlled study; Cell Membrane; Cell Membrane; nonhuman; animal tissue; animal model; animal experiment; Reaction Time; drug delivery system; minimum inhibitory concentration; drug mechanism; binding affinity; physical chemistry; drug structure; zeolite; antiinfective agent; antibiotic agent; ANTIMICROBIAL ACTIVITY; antibacterial activity; Biofilm; Biofilm; anti-bacterial agents; bactericidal activity; bacterial growth; antibiotic sensitivity; kanamycin; drug synthesis; incubation time; Fourier transform infrared spectroscopy; X ray diffraction; Anti-Infective Agents; colony forming unit; Static Electricity; Molecular docking; abdominal infection; RODENT MODEL; Drug-resistant bacteria; Aeromonas veronii; Zeolitic imidazolate framework; Bacterial viability; pyrithione; multidrug resistant bacterium; zeolites; SmpB protein}, year = {2023}, eissn = {2373-8227}, pages = {507-517} } @misc{MTMT:34135046, title = {Comprehensive analysis of FZD7 in immune infiltration and prognosis of pan-cancer and validation in hepatocellular carcinoma}, url = {https://m2.mtmt.hu/api/publication/34135046}, author = {Yu, Huajing and Guan, Chengjian and Qu, Guangzhen and Wei, Luyang and Liu, Shanshan and Jing, Chao and Yin, Danyang and Lin, Huajun and Zhang, Xiaodong and Rao, Quan and Wu, Hongwei and Liu, Kun and Wang, Dong and Zhang, Zhongtao and Guo, Wei}, doi = {10.21203/rs.3.rs-2642508/v1}, unique-id = {34135046}, abstract = {Abstract Background Frizzled 7, a G protein-coupled receptor, can regulate cell proliferation, migration, and tumorigenesis. The effect of FZD7 on prognosis and the immune microenvironment in pan-cancer remains elusive. Hence, we plan to provide insight into FZD7's role in pan-cancer. Methods FZD7 expression was analyzed by integrating RNA sequencing data from TCGA and GEO databases. Furthermore, we elucidated the correlation between FZD7 and prognosis, mutation landscape, immune infiltration, and biological function by analyzing multiple databases in pan-cancer. A prognostic risk model was constructed based on the sequencing data of HCC in the TCGA database and its validity was verified in the GEO database. In addition, reverse transcription-polymerase chain reaction assays were performed to validate FZD7 expression in HCC tumor tissues. Results Compared with adjacent noncancerous tissues, FZD7 was upregulated in several tumor tissues, especially HCC, and its elevated expression account for tumor progression and poor prognosis. Significant associations were found between FZD7 expression and TMB or MSI in several tumors. Immune infiltration analysis revealed a close link between FZD7 expression and the presence of myeloid-derived suppressor cells, T cell regulatory, as well as the cancer-associated fibroblasts. However, it negatively correlated with CD4 + Th1 cell and CD4 + Th2 infiltration. FZD7-related functional genes were successfully incorporated into the construction and validation of an HCC prognostic risk model. Conclusion Our study indicated that FZD7 is involved in regulating the progression of several tumors and immune infiltration, while it can serve as an effective prognosis biomarker in pan-cancer, especially HCC. This could shed light on tumor therapy.}, year = {2023} } @article{MTMT:32850816, title = {Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides}, url = {https://m2.mtmt.hu/api/publication/32850816}, author = {Bhattacharjya, S. and Mohid, S.A. and Bhunia, A.}, doi = {10.3390/ijms23094558}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {32850816}, issn = {1661-6596}, abstract = {Global rise of infections and deaths caused by drug-resistant bacterial pathogens are among the unmet medical needs. In an age of drying pipeline of novel antibiotics to treat bacterial infections, antimicrobial peptides (AMPs) are proven to be valid therapeutics modalities. Direct in vivo applications of many AMPs could be challenging; however, works are demonstrating encouraging results for some of them. In this review article, we discussed 3-D structures of potent AMPs e.g., polymyxin, thanatin, MSI, protegrin, OMPTA in complex with bacterial targets and their mode of actions. Studies on human peptide LL37 and de novo-designed peptides are also discussed. We have focused on AMPs which are effective against drug-resistant Gram-negative bacteria. Since treatment options for the infections caused by super bugs of Gram-negative bacteria are now extremely limited. We also summarize some of the pertinent challenges in the field of clinical trials of AMPs. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.}, keywords = {antibiotics; Antimicrobial peptides (AMPs); Lipopolysaccharide (LPS); MDR gram negative bacteria; Mechanism of AMPs; multidrug resistant (MDR) bacteria}, year = {2022}, eissn = {1422-0067} } @article{MTMT:34136805, title = {Novel foldameric peptide adjuvants counter antimicrobial resistance via promoting membrane hyperpolarization}, url = {https://m2.mtmt.hu/api/publication/34136805}, author = {Bhaumik, Kaushik Nath and Hetenyi, Anasztazia and Olajos, Gabor and Martins, Ana and Spohn, Reka and Nemeth, Lukacs and Jojart, Balazs and Szili, Petra and Dunai, Anett and Jangir, Pramod K. and Daruka, Leila and Foldesi, Imre and Kata, Diana and Pal, Csaba and Martinek, Tamas A.}, journal-iso = {J PEPT SCI}, journal = {JOURNAL OF PEPTIDE SCIENCE}, volume = {28}, unique-id = {34136805}, issn = {1075-2617}, year = {2022}, eissn = {1099-1387} } @article{MTMT:32493048, title = {Rationally designed foldameric adjuvants enhance antibiotic efficacy via promoting membrane hyperpolarization}, url = {https://m2.mtmt.hu/api/publication/32493048}, author = {Nath Bhaumik, Kaushik and Hetényi, Anasztázia and Olajos, Gábor and Martins, Ana and Spohn, Réka and Németh, Lukács and Jójárt, Balázs and Szili, Petra and Dunai, Anett and Jangir, Pramod Kumar and Daruka, Lejla and Földesi, Imre and Kata, Diána and Pál, Csaba and Martinek, Tamás}, doi = {10.1039/D1ME00118C}, journal-iso = {MOL SYST DES ENG}, journal = {MOLECULAR SYSTEMS DESIGN & ENGINEERING}, volume = {7}, unique-id = {32493048}, issn = {2058-9689}, abstract = {The negative membrane potential of bacterial cells influences crucial cellular processes. Inspired by the molecular scaffold of the antimicrobial peptide PGLa, we have developed antimicrobial foldamers with a computer-guided design strategy. The novel PGLa analogues induce sustained membrane hyperpolarization. When co-administered as an adjuvant, the resulting compounds - PGLb1 and PGLb2 - have substantially reduced the level of antibiotic resistance of multi-drug resistant Escherichia coli, Klebsiella pneumoniae and Shigella flexneri clinical isolates. The observed antibiotic potentiation was mediated by hyperpolarization of the bacterial membrane caused by the alteration of cellular ion transport. Specifically, PGLb1 and PGLb2 are selective ionophores that enhance the Goldman-Hodgkin-Katz potential across the bacterial membrane. These findings indicate that manipulating bacterial membrane electrophysiology could be a valuable tool to overcome antimicrobial resistance.}, year = {2022}, eissn = {2058-9689}, pages = {21-33}, orcid-numbers = {Hetényi, Anasztázia/0000-0001-8080-6992; Olajos, Gábor/0000-0002-2479-4891; Jangir, Pramod Kumar/0000-0001-8330-0655; Földesi, Imre/0000-0002-3329-8136; Kata, Diána/0000-0002-4432-9380; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:32850855, title = {An ultrasensitive microfluidic approach reveals correlations between the physico-chemical and biological activity of experimental peptide antibiotics}, url = {https://m2.mtmt.hu/api/publication/32850855}, author = {Cama, J. and Al, Nahas K. and Fletcher, M. and Hammond, K. and Ryadnov, M.G. and Keyser, U.F. and Pagliara, S.}, doi = {10.1038/s41598-022-07973-z}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {12}, unique-id = {32850855}, issn = {2045-2322}, abstract = {Antimicrobial resistance challenges the ability of modern medicine to contain infections. Given the dire need for new antimicrobials, polypeptide antibiotics hold particular promise. These agents hit multiple targets in bacteria starting with their most exposed regions—their membranes. However, suitable approaches to quantify the efficacy of polypeptide antibiotics at the membrane and cellular level have been lacking. Here, we employ two complementary microfluidic platforms to probe the structure–activity relationships of two experimental series of polypeptide antibiotics. We reveal strong correlations between each peptide’s physicochemical activity at the membrane level and biological activity at the cellular level. We achieve this knowledge by assaying the membranolytic activities of the compounds on hundreds of individual giant lipid vesicles, and by quantifying phenotypic responses within clonal bacterial populations with single-cell resolution. Our strategy proved capable of detecting differential responses for peptides with single amino acid substitutions between them, and can accelerate the rational design and development of peptide antimicrobials. © 2022, The Author(s).}, keywords = {BACTERIA; Chemistry; structure-activity relationship; bacterium; antiinfective agent; anti-bacterial agents; structure activity relation; Microfluidics; Microfluidics; Anti-Infective Agents; Antimicrobial Cationic Peptides; antimicrobial cationic peptide}, year = {2022}, eissn = {2045-2322} } @{MTMT:34075837, title = {Herbal Antibiotics for Treating Drug‐Resistant Bacteria}, url = {https://m2.mtmt.hu/api/publication/34075837}, author = {Chen, Haixia and Li, Shuqin}, booktitle = {Herbal Drugs for the Management of Infectious Diseases}, doi = {10.1002/9781119818779.ch2}, unique-id = {34075837}, year = {2022}, pages = {23-53} } @article{MTMT:33030708, title = {Antimicrobial peptides: Sustainable application informed by evolutionary constraints}, url = {https://m2.mtmt.hu/api/publication/33030708}, author = {Chen, X. and Han, J. and Cai, X. and Wang, S.}, doi = {10.1016/j.biotechadv.2022.108012}, journal-iso = {BIOTECHNOL ADV}, journal = {BIOTECHNOLOGY ADVANCES}, volume = {60}, unique-id = {33030708}, issn = {0734-9750}, year = {2022}, eissn = {1873-1899} } @article{MTMT:32850813, title = {Integrated evolutionary analysis reveals the resistance risk to antimicrobial peptides in Staphylococcus aureus}, url = {https://m2.mtmt.hu/api/publication/32850813}, author = {Chen, X. and Han, J. and Wang, S.}, doi = {10.1016/j.foodcont.2022.108966}, journal-iso = {FOOD CONTROL}, journal = {FOOD CONTROL}, volume = {138}, unique-id = {32850813}, issn = {0956-7135}, abstract = {The safety risks of antimicrobial peptide (AMP) resistance have never been properly understood. Herein, we comprehensively investigated the evolution of resistance to AMPs in Staphylococcus aureus using piscidin1 (PIS-1) and piscidin3 (PIS-3) as archetypes, in which they were both combined with cell membranes via a common structural motif but vary in permeabilizing actions. The results demonstrated that the bacterial strain acquired limited resistance to PIS-3 compared to PIS-1. However, the PIS-3-induced strain developed parlous co-resistance toward PIS-1, ampicillin, ofloxacin, rifampicin, tetracycline, vancomycin, and polymyxin B. Based on the results of the chemiluminescence method, transcriptome sequencing and proteomic analysis, the generation of bacterial co-resistance was affiliated with decreased cell membrane permeability, mainly involving the regulation of the two-component system, ATP-binding cassette transporters and phosphotransferase system. These findings highlight concerns that AMPs could trigger a new crisis of drug resistance in food packaging, feed additives, and the agricultural environment. © 2022 Elsevier Ltd}, keywords = {ANTIMICROBIAL PEPTIDES; Antibiotic resistance; Antibiotic alternatives; transcriptomics and proteomics; Co-resistance}, year = {2022}, eissn = {1873-7129} } @article{MTMT:32734830, title = {Membrane-Active Antibacterial Agents Based on Calix[4]arene Derivatives: Synthesis and Biological Evaluation}, url = {https://m2.mtmt.hu/api/publication/32734830}, author = {Fang, Shanfang and Dang, Yuan-Ye and Li, Haizhou and Li, Hongxia and Liu, Jiayong and Zhong, Rongcui and Chen, Yongzhi and Liu, Shouping and Lin, Shuimu}, doi = {10.3389/fchem.2022.816741}, journal-iso = {FRONT CHEM}, journal = {FRONTIERS IN CHEMISTRY}, volume = {10}, unique-id = {32734830}, issn = {2296-2646}, year = {2022}, eissn = {2296-2646} } @article{MTMT:33135935, title = {Editorial: Antimicrobial peptides and mRNA therapy: Clinical, Veterinary, and plant pathology perspectives with special attention to combatting MDR pathogens}, url = {https://m2.mtmt.hu/api/publication/33135935}, author = {Fodor, András and Méhi, Orsolya Katinka and Brivio, Maurizio}, doi = {10.3389/fmicb.2022.1030874}, journal-iso = {FRONT MICROBIOL}, journal = {FRONTIERS IN MICROBIOLOGY}, volume = {13}, unique-id = {33135935}, issn = {1664-302X}, year = {2022}, eissn = {1664-302X}, orcid-numbers = {Méhi, Orsolya Katinka/0009-0004-7918-913X} } @article{MTMT:32742483, title = {Type Strains of Entomopathogenic Nematode-Symbiotic Bacterium Species, Xenorhabdus szentirmaii (EMC) and X. budapestensis (EMA), Are Exceptional Sources of Non-Ribosomal Templated, Large-Target-Spectral, Thermotolerant-Antimicrobial Peptides (by Both), and Iodinin (by EMC)}, url = {https://m2.mtmt.hu/api/publication/32742483}, author = {Fodor, András and Gualtieri, Maxime and Zeller, Matthias and Tarasco, Eustachio and Klein, Michael G. and Fodor, Andrea M. and Haynes, Leroy and Lengyel, Katalin and Forst, Steven A. and Furgani, Ghazala M. and Karaffa, Levente and Vellai, Tibor}, doi = {10.3390/pathogens11030342}, journal-iso = {PATHOGENS}, journal = {PATHOGENS}, volume = {11}, unique-id = {32742483}, abstract = {Antimicrobial multidrug resistance (MDR) is a global challenge, not only for public health, but also for sustainable agriculture. Antibiotics used in humans should be ruled out for use in veterinary or agricultural settings. Applying antimicrobial peptide (AMP) molecules, produced by soil-born organisms for protecting (soil-born) plants, seems a preferable alternative. The natural role of peptide-antimicrobials, produced by the prokaryotic partner of entomopathogenic-nematode/bacterium (EPN/EPB) symbiotic associations, is to sustain monoxenic conditions for the EPB in the gut of the semi-anabiotic infective dauer juvenile (IJ) EPN. They keep pathobiome conditions balanced for the EPN/EPB complex in polyxenic (soil, vanquished insect cadaver) niches. Xenorhabdus szentirmaii DSM16338(T) (EMC), and X. budapestensis DSM16342(T) (EMA), are the respective natural symbionts of EPN species Steinernema rarum and S. bicornutum. We identified and characterized both of these 15 years ago. The functional annotation of the draft genome of EMC revealed 71 genes encoding non-ribosomal peptide synthases, and polyketide synthases. The large spatial Xenorhabdus AMP (fabclavine), was discovered in EMA, and its biosynthetic pathway in EMC. The AMPs produced by EMA and EMC are promising candidates for controlling MDR prokaryotic and eukaryotic pathogens (bacteria, oomycetes, fungi, protozoa). EMC releases large quantity of iodinin (1,6-dihydroxyphenazine 5,10-dioxide) in a water-soluble form into the media, where it condenses to form spectacular water-insoluble, macroscopic crystals. This review evaluates the scientific impact of international research on EMA and EMC.}, year = {2022}, eissn = {2076-0817}, orcid-numbers = {Tarasco, Eustachio/0000-0001-6310-186X; Karaffa, Levente/0000-0002-3077-8732; Vellai, Tibor/0000-0002-3520-2572} } @mastersthesis{MTMT:34075909, title = {Caracterización molecular y de sensibilidad in vitro a antibióticos y péptidos derivados de catelicidina como agentes antimicrobianos frente a aislamientos clínicos de Staphylococcus aureus procedentes de la ciudad de Bogotá D.C.}, url = {https://m2.mtmt.hu/api/publication/34075909}, author = {Fonseca Fernández, Angie Lorena}, unique-id = {34075909}, year = {2022} } @article{MTMT:32868164, title = {The EnvZ/OmpR Two-Component System Regulates the Antimicrobial Activity of TAT-RasGAP(317-326) and the Collateral Sensitivity to Other Antibacterial Agents}, url = {https://m2.mtmt.hu/api/publication/32868164}, author = {Georgieva, Maria and Heinonen, Tytti and Hargraves, Simone and Pillonel, Trestan and Widmann, Christian and Jacquier, Nicolas}, doi = {10.1128/spectrum.02009-21}, journal-iso = {MICROBIOL SPEC}, journal = {MICROBIOLOGY SPECTRUM}, volume = {10}, unique-id = {32868164}, issn = {2165-0497}, abstract = {Antimicrobial peptides (AMP) are promising alternatives to classical antibiotics in the fight against antibiotic resistance. Resistance toward antimicrobial peptides can occur, but little is known about the mechanisms driving this phenomenon. The rapid emergence of antibiotic-resistant bacteria poses a serious threat to public health worldwide. Antimicrobial peptides (AMPs) are promising antibiotic alternatives; however, little is known about bacterial mechanisms of AMP resistance and the interplay between AMP resistance and the bacterial response to other antimicrobials. In this study, we identified Escherichia coli mutants resistant to the TAT-RasGAP(317-326) antimicrobial peptide and found that resistant bacteria show collateral sensitivity to other AMPs and antibacterial agents. We determined that resistance to TAT-RasGAP(317-326) peptide arises through mutations in the histidine kinase EnvZ, a member of the EnvZ/OmpR two-component system responsible for osmoregulation in E. coli. In particular, we found that TAT-RasGAP(317-326) binding and entry is compromised in E. coli peptide-resistant mutants. We showed that peptide resistance is associated with transcriptional regulation of a number of pathways and EnvZ-mediated resistance is dependent on the OmpR response regulator but is independent of the OmpC and OmpF outer membrane porins. Our findings provide insight into the bacterial mechanisms of TAT-RasGAP(317-326) resistance and demonstrate that resistance to this AMP is associated with collateral sensitivity to other antibacterial agents. IMPORTANCE Antimicrobial peptides (AMP) are promising alternatives to classical antibiotics in the fight against antibiotic resistance. Resistance toward antimicrobial peptides can occur, but little is known about the mechanisms driving this phenomenon. Moreover, there is limited knowledge on how AMP resistance relates to the bacterial response to other antimicrobial agents. Here, we address these questions in the context of the antimicrobial peptide TAT-RasGAP(317-326). We show that resistant Escherichia coli strains can be selected and do not show resistance to other antimicrobial agents. Resistance is caused by a mutation in a regulatory pathway, which lowers binding and entry of the peptide in E. coli. Our results highlight a mechanism of resistance that is specific to TAT-RasGAP(317-326). Further research is required to characterize these mechanisms and to evaluate the potential of antimicrobial combinations to curb the development of antimicrobial resistance.}, keywords = {PEPTIDES; IN-VIVO; ESCHERICHIA-COLI; PHOSPHATASE-ACTIVITY; Escherichia coli; Antibiotic resistance; Osmoregulation; ANTIBIOTIC-RESISTANCE; two-component system; Antimicrobial peptide; CROSS-RESISTANCE; BACTERIAL-RESISTANCE; ENVZ}, year = {2022}, eissn = {2165-0497}, orcid-numbers = {Jacquier, Nicolas/0000-0002-1974-8161} } @article{MTMT:32850866, title = {The Remarkable Innate Resistance of Burkholderia bacteria to Cationic Antimicrobial Peptides: Insights into the Mechanism of AMP Resistance}, url = {https://m2.mtmt.hu/api/publication/32850866}, author = {Ghimire, J. and Guha, S. and Nelson, B.J. and Morici, L.A. and Wimley, W.C.}, doi = {10.1007/s00232-022-00232-2}, journal-iso = {J MEMBRANE BIOL}, journal = {JOURNAL OF MEMBRANE BIOLOGY}, volume = {255}, unique-id = {32850866}, issn = {0022-2631}, abstract = {Gram-negative bacteria belonging to the genus Burkholderia are remarkably resistant to broad-spectrum, cationic, antimicrobial peptides (AMPs). It has been proposed that this innate resistance is related to changes in the outer membrane lipopolysaccharide (OM LPS), including the constitutive, essential modification of outer membrane Lipid A phosphate groups with cationic 4-amino-4-deoxy-arabinose. This modification reduces the overall negative charge on the OM LPS which may change the OM structure and reduce the binding, accumulation, and permeation of cationic AMPs. Similarly, the Gram-negative pathogen Pseudomonas aeruginosa can quickly become resistant to many AMPs by multiple mechanisms, frequently, including activation of the arn operon, which leads, transiently, to the same modification of Lipid A. We recently discovered a set of synthetically evolved AMPs that do not invoke any resistance in P. aeruginosa over multiple passages and thus are apparently not inhibited by aminorabinosylation of Lipid A in P. aeruginosa. Here we test these resistance-avoiding peptides, within a set of 18 potent AMPs, against Burkholderia thailandensis. We find that none of the AMPs tested have measurable activity against B. thailandensis. Some were inactive at concentrations as high as 150 μM, despite all having sterilizing activity at ≤ 10 μM against a panel of common, human bacterial pathogens, including P. aeruginosa. We speculate that the constitutive modification of Lipid A in members of the Burkholderia genus is only part of a broader set of modifications that change the architecture of the OM to provide such remarkable levels of resistance to cationic AMPs. Graphical Abstract: [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.}, keywords = {ANTIMICROBIAL PEPTIDES; outer membrane; Burkholderia}, year = {2022}, eissn = {1432-1424}, pages = {503-511} } @article{MTMT:33087033, title = {The antimicrobial peptide DGL13K is active against drug-resistant gram-negative bacteria and sub-inhibitory concentrations stimulate bacterial growth without causing resistance}, url = {https://m2.mtmt.hu/api/publication/33087033}, author = {Gorr, S.-U. and Brigman, H.V. and Anderson, J.C. and Hirsch, E.B.}, doi = {10.1371/journal.pone.0273504}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {17}, unique-id = {33087033}, issn = {1932-6203}, abstract = {Antimicrobial peptides may be alternatives to traditional antibiotics with reduced bacterial resistance. The antimicrobial peptide GL13K was derived from the salivary protein BPIFA2. This study determined the relative activity of the L-and D-enantiomers of GL13K to wild-type and drug-resistant strains of three gram-negative species and against Pseudomonas aeruginosa biofilms. DGL13K displayed in vitro activity against extended-spectrum beta-lactamase (ESBL)-producing and Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (MICs 16-32 μg/ml), MDR and XDR P. aeruginosa, and XDR Acinetobacter baumannii carrying metallo-beta-lactamases (MICs 8-32 μg/ml). P. aeruginosa showed low inherent resistance to DGL13K and the increased metabolic activity and growth caused by sub-MIC concentrations of GL13K peptides did not result in acquired bacterial resistance. Daily treatment for approximately two weeks did not increase the MIC of DGL13K or cause cross-resistance between LGL13K and DGL13K. These data suggest that DGL13K is a promising antimicrobial peptide candidate for further development. © 2022 Gorr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.}, year = {2022}, eissn = {1932-6203} } @article{MTMT:32598572, title = {Pathogenicity and innate response to Avibacterium paragallinarum in chickens}, url = {https://m2.mtmt.hu/api/publication/32598572}, author = {Guo, M. and Liu, D. and Chen, X. and Wu, Y. and Zhang, X.}, doi = {10.1016/j.psj.2021.101523}, journal-iso = {POULTRY SCI}, journal = {POULTRY SCIENCE}, volume = {101}, unique-id = {32598572}, issn = {0032-5791}, abstract = {Infectious coryza (IC) is an acute infectious upper respiratory disease in chickens. Recently, the prevalence of IC has increased in China. In this study, to clarify the pathogenic mechanism and innate immune response of Avibacterium paragallinarum (A. paragallinarum), an infection experiment with A. paragallinarum was conducted. Our results showed that the whole course of IC was approximately 7 d. The clinical signs score was highest at 3 dpi and decreased from 5 dpi. A large amount of mucus and exudates was found in the infraorbital sinuses and nasal cavity. The A. paragallinarum contents in blood remained the highest, reaching 9.16 × 105 CFU/g at 5 dpi, which indicated that A. paragallinarum could rapidly invade the host, replicate in the blood and cause bacteremia. A. paragallinarum targets the upper respiratory tract. The infiltration of inflammatory cells, macrophages, and heterophilic granulocytes was only observed in the nasal cavity and infraorbital sinus. The Tlr4 and Nod1 pathways were activated and induced proinflammatory responses in chickens after infection with A. paragallinarum. The expression of Il1β and Il6 in the nasal cavity was significantly higher than that in the spleen, and it was consistent with the gross lesions and pathological changes. In particular, the expression of Il6 increased 229.07-fold at 1 dpi in the nasal cavity and increased 3.12-fold in the spleen. The high level of proinflammatory cytokines in the nasal cavity at an early stage of infection may be the main factor related to acute upper respiratory inflammation in chickens. These findings provide a reference for the occurrence and development of diseases mediated by A. paragallinarum. © 2021 The Authors}, keywords = {innate immunity; pathogenicity; chicken; infectious coryza; Avibacterium paragallinarum}, year = {2022}, eissn = {1525-3171} } @article{MTMT:33087035, title = {Metal organic framework-based antibacterial agents and their underlying mechanisms}, url = {https://m2.mtmt.hu/api/publication/33087035}, author = {Han, D. and Liu, X. and Wu, S.}, doi = {10.1039/d2cs00460g}, journal-iso = {CHEM SOC REV}, journal = {CHEMICAL SOCIETY REVIEWS}, volume = {51}, unique-id = {33087035}, issn = {0306-0012}, abstract = {Bacteria, as the most abundant living organisms, have always been a threat to human life until the development of antibiotics. However, with the wide use of antibiotics over a long time, bacteria have gradually gained tolerance to antibiotics, further aggravating threat to human beings and environmental safety significantly. In recent decades, new bacteria-killing methods based on metal ions, hyperthermia, free radicals, physical pricks, and the coordination of several multi-mechanisms have attracted increasing attention. Consequently, multiple types of new antibacterial agents have been developed. Among them, metal organic frameworks (MOFs) appear to play an increasingly important role. The unique characteristics of MOFs make them suitable multiple-functional platforms. By selecting the appropriate metastable coordination bonds, MOFs can act as reservoirs and release antibacterial metal ions or organic linkers; by constructing a porous structure, MOFs can act as carriers for multiple types of agents and achieve slow and sustained release; and by designing their composition and the pore structure precisely, MOFs can be endowed with properties to produce heat and free radicals under stimulation. Importantly, in combination with other materials, MOFs can act as a platform to kill bacteria effectively through the synergistic effect of multiple types of mechanisms. In this review, we focus on the recent development of MOF-based antibacterial agents, which are classified according to their antibacterial mechanisms. © 2022 The Royal Society of Chemistry.}, keywords = {Humans; BACTERIA; human; IONS; Chemistry; Free Radicals; METALS; METALS; METAL; Porosity; Porosity; pore structure; ION; antibiotics; antiinfective agent; anti-bacterial agents; metal ions; Organic polymers; Human being; Living organisms; METAL-ORGANIC FRAMEWORKS; METAL-ORGANIC FRAMEWORKS; Metalorganic frameworks (MOFs); coordination bonds; Metal organic framework; environmental safety; Human lives; metals ions; Metastables; Antibacterial metals; Multi mechanisms}, year = {2022}, eissn = {1460-4744}, pages = {7138-7169} } @article{MTMT:33597300, title = {Combating Escherichia coli O157:H7 with Functionalized Chickpea-Derived Antimicrobial Peptides}, url = {https://m2.mtmt.hu/api/publication/33597300}, author = {He, Q. and Yang, Z. and Zou, Z. and Qian, M. and Wang, X. and Zhang, X. and Yin, Z. and Wang, J. and Ye, X. and Liu, D. and Guo, M.}, doi = {10.1002/advs.202205301}, journal-iso = {ADV SCI}, journal = {ADVANCED SCIENCE}, unique-id = {33597300}, abstract = {The rapid dissemination of antibiotic resistance accelerates the desire for new antibacterial agents. Here, a class of antimicrobial peptides (AMPs) is designed by modifying the structural parameters of a natural chickpea-derived AMP–Leg2, termed “functionalized chickpea-derived Leg2 antimicrobial peptides” (FCLAPs). Among the FCLAPs, KTA and KTR show superior antibacterial efficacy against the foodborne pathogen Escherichia coli (E. coli) O157:H7 (with MICs in the range of 2.5–4.7 µmol L−1) and demonstrate satisfactory feasibility in alleviating E. coli O157:H7-induced intestinal infection. Additionally, the low cytotoxicity along with insusceptibility to antimicrobial resistance increases the potential of FCLAPs as appealing antimicrobials. Combining the multi-omics profiling andpeptide-membrane interaction assays, a unique dual-targeting mode of action is characterized. To specify the antibacterial mechanism, microscopical observations, membrane-related physicochemical properties studies, and mass spectrometry assays are further performed. Data indicate that KTA and KTR induce membrane damage by initially targeting the lipopolysaccharide (LPS), thus promoting the peptides to traverse the outer membrane. Subsequently, the peptides intercalate into the peptidoglycan (PGN) layer, blocking its synthesis, and causing a collapse of membrane structure. These findings altogether imply the great potential of KTA and KTR as promising antibacterial candidates in combating the growing threat of E. coli O157:H7. © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.}, keywords = {PEPTIDES; MEMBRANES; PHYSICOCHEMICAL PROPERTIES; Escherichia coli; Mass spectrometry; ANTIMICROBIAL PEPTIDES; Functionalized; Food products; Mechanism of action; Antimicrobial peptide; Food-borne pathogens; antibiotics resistance; Escherichia coli O157:H7; Escherichia coli O157:H7; Antimicrobial mechanisms; dual-targeting mechanism of action; dual-targeting mechanism of action; membrane-mediated antimicrobial mechanism; membrane-mediated antimicrobial mechanism; foodborne pathogen intervention; foodborne pathogen intervention}, year = {2022}, eissn = {2198-3844} } @article{MTMT:32868165, title = {Unique mechanistic insights into pathways associated with the synergistic activity of polymyxin B and caspofungin against multidrug- resistant Klebsiella pneumoniae}, url = {https://m2.mtmt.hu/api/publication/32868165}, author = {Hussein, Maytham and Wong, Labell J. M. and Zhao, Jinxin and Rees, Vanessa E. and Allobawi, Rafah and Sharma, Rajnikant and Rao, Gauri G. and Baker, Mark and Li, Jian and Velkov, Tony}, doi = {10.1016/j.csbj.2022.02.021}, journal-iso = {CSBJ}, journal = {COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL}, volume = {20}, unique-id = {32868165}, issn = {2001-0370}, abstract = {Klebsiella pneumoniae is an opportunistic Gram-negative pathogen causing nosocomial infections. K. pneumoniae rapidly acquires antibiotic resistance and is known as a reservoir for resistance genes. Polymyxins remain effective as a last-line therapy against infections caused by multidrug-resistant (MDR) K. pneumoniae; however, resistance to polymyxins emerges rapidly with monotherapy. Synergistic combinations of polymyxins with FDA-approved non-antibiotics are a novel approach to preserve its efficacy whilst minimising the emergence of polymyxin resistance in K. pneumoniae. This study aimed to investigate the synergistic antibacterial activity of polymyxin B in combination with the anti fungal caspofungin against K. pneumoniae. The combination of polymyxin B and caspofungin showed marked synergistic antibacterial killing activity in checkerboard broth microdilution and static time kill assays at clinically relevant concentrations at early (0.5 and 1 h) and later (4 h) time points. The potential bacterial killing mechanism of the combination was studied against K. pneumoniae FADDIKP001 using metabolomics and transcriptomics studies at 0.5, 1 and 4 h. The key pathways involved in the synergistic killing action of the combination were cell wall assembly (peptidoglycan and lipopolysaccharide biosynthesis), central carbon metabolism (glycolysis, pentose phosphate pathway and tricarboxylic acid cycle) and fatty acid biosynthesis. Moreover, the combination inhibited the most common bacterial virulence pathway (phosphotransferase system) as well as the multi-resistant efflux mechanisms, including ATP-binding cassette (ABC) transporter pathway. Overall, this study sheds light on the possibility of a polymyxin-caspofungin combination for the treatment of infections caused by K. pneumoniae and may help repurpose FDA-approved caspofungin against MDR K. pneumoniae infections.(c) 2022 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).}, keywords = {PROTEIN; LIPOPOLYSACCHARIDE; biosynthesis; EPIDEMIOLOGY; antibacterial activity; caspofungin; transcriptomics; metabolomics; polymyxin; PHASE-II; Antimicrobial peptide; colistin; MASS-SPECTROMETRY DATA; Biochemistry & Molecular Biology; Gram-negative; phosphotransferase system}, year = {2022}, eissn = {2001-0370}, pages = {1077-1087}, orcid-numbers = {Li, Jian/0000-0001-7953-8230} } @article{MTMT:34776035, title = {Recent research progress of biologically active peptides}, url = {https://m2.mtmt.hu/api/publication/34776035}, author = {Kang, L. and Han, T. and Cong, H. and Yu, B. and Shen, Y.}, doi = {10.1002/biof.1822}, journal-iso = {BIOFACTORS}, journal = {BIOFACTORS}, volume = {48}, unique-id = {34776035}, issn = {0951-6433}, year = {2022}, eissn = {1872-8081}, pages = {575-596} } @mastersthesis{MTMT:34110556, title = {Phage infection reinstates antibiotic sensitivity in MDR Pseudomonas aeruginosa: A study on phage and bacterial evolution}, url = {https://m2.mtmt.hu/api/publication/34110556}, author = {Koderi Valappil, Sarshad}, doi = {10.14232/phd.11330}, publisher = {Universití of Szeged}, unique-id = {34110556}, abstract = {The emergence of antibiotic resistance among bacterial pathogens is a significant public health threat affecting humans worldwide. In Europe, Pseudomonas aeruginosa contributes to almost 9% of overall multi-drug-resistant (MDR) infections. Alternative methods for controlling MDR pathogens have been explored for several decades. Bacteriophage therapy is one of the oldest and most efficient alternative solutions. The study described in this thesis began with the isolation and characterization of 25 MDR P. aeruginosa clinical strains and eigth novel lytic phages. The investigation disclosed the infection with two phage isolates, PIAS and PAPSZ1, led to the sequential appearance of phage-resistant colonies with two phenotypes (green and brown). We examined the evolutionary basis for the two types of mutants and uncovered phage mutants capable of infecting green mutants. Simultaneously we also learned that PIAS phage infected the host via the OrpM-MexXY system involved in drug efflux. Thus, the PIAS-resistant mutants decreased the minimum inhibitory concentrations (MIC) for several non-effective antibiotics. After this new insight into the evolutionary arms race between hosts and phages, we decided to use this window to comprehensively eradicate mutants by treating MDR strain with previously resistant antibiotics combined with PIAS phage. The in vitro study with PIAS phage-antibiotic combination completely prevented the formation and growth of mutants. We tested the same strategy in an in vivo rescue experiment in the mouse lung infection model, when combined with PIAS phage and fosfomycin. The combination therapy saved 75% of the animals. Later, we used PAPSZ1 phage to investigate whether phage mutants can suppress bacterial resistance. We isolated multiple PAPSZ1 mutants after a continuous infection cycle, which can block or suppress bacterial resistance and mutant formation and broaden the host specificity of the phages. Phages like PIAS and PAPSZ1 offer a unique window that can exploit to eradicate MDR bacteria. This study highlights the importance of preliminary and detailed examinations of phage-host bacterium interactions preceding the application of a given phage. The experimental data in this thesis shows that studying phage-host bacterium interactions and coevolution will help to utilize phage therapy’s full potential when treating MDR infections.}, year = {2022} } @article{MTMT:33155416, title = {Antibiotic combinations reduce Staphylococcus aureus clearance}, url = {https://m2.mtmt.hu/api/publication/33155416}, author = {Lázár, Viktória and Snitser, Olga and Barkan, Daniel and Kishony, Roy}, doi = {10.1038/s41586-022-05260-5}, journal-iso = {NATURE}, journal = {NATURE}, volume = {610}, unique-id = {33155416}, issn = {0028-0836}, year = {2022}, eissn = {1476-4687}, pages = {540-546}, orcid-numbers = {Kishony, Roy/0000-0002-5013-5072} } @article{MTMT:32598571, title = {Synthesis and bioactivities of new N-terminal dipeptide mimetics with aromatic amide moiety: Broad-spectrum antibacterial activity and high antineoplastic activity}, url = {https://m2.mtmt.hu/api/publication/32598571}, author = {Li, H. and Fu, S. and Liu, L. and Yuan, X. and Wang, Y. and Zhang, C. and Dong, H. and Satoh, T.}, doi = {10.1016/j.ejmech.2021.113977}, journal-iso = {EUR J MED CHEM}, journal = {EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY}, volume = {228}, unique-id = {32598571}, issn = {0223-5234}, abstract = {The increasingly growing epidemics of multidrug-resistant bacteria are becoming severe public health threat. There is in an urgent need to develop new antibacterial agents with broad-spectrum antibacterial activity and high selectivity. Here, a series of N-terminal dipeptide mimetics with an aromatic amide moiety were synthesized from amino acids. The effects of amino acid type and aromatic moiety on the biological activities of the mimetics were evaluated. The dipeptide mimetics not only showed significant broad-spectrum antibacterial activity against Gram-negative (Escherichia coli and Klebsiella pneumoniae), Gram-positive (Staphylococcus aureus) and drug-resistant bacterium MRSA (methicillin-resistant S. aureus) but also demonstrated high selectivity for S. aureus versus mammalian erythrocytes. The coupling product of L-valine with p-alkynylaniline (dipeptide mimetic 7) exhibited the best antibacterial activities with minimum inhibitory concentration (MIC) ranging from 2.5 to 5 μg/mL. Moreover, the bactericidal kinetics and multi-passage resistance tests indicated that the mimetic 7 both rapidly killed bacteria and had a low probability of emergence of antimalarial resistance. Meanwhile, the mimetic 7 possessed the ability to both inhibit bacterial biofilm formation and eradicate mature biofilm. The depolarization and destruction of the bacterial cell membrane is the main sterilization mechanism, which hinders the propensity to develop bacterial resistance. Furthermore, the mimetic 7 also showed good antineoplastic activity against gastric cancer cell (SGC 7901, IC50 = 70.8 μg/mL), while it had very low toxicity to mammalian cell (L929). The mimetics bear considerable potential to be used as antibacterial and anticancer agents to combat antibiotic resistance. © 2021 Elsevier Masson SAS}, keywords = {ANTIBACTERIAL; amino acids; antineoplastic; Dipeptide mimetics; Low cytotoxicity}, year = {2022}, eissn = {1768-3254} } @article{MTMT:32850863, title = {A Cationic Amphipathic Tilapia Piscidin 4 Peptide-Based Antimicrobial Formulation Promotes Eradication of Bacterial Vaginosis-Associated Bacterial Biofilms}, url = {https://m2.mtmt.hu/api/publication/32850863}, author = {Lin, W.-C. and Chen, Y.-R. and Chuang, C.-M. and Chen, J.-Y.}, doi = {10.3389/fmicb.2022.806654}, journal-iso = {FRONT MICROBIOL}, journal = {FRONTIERS IN MICROBIOLOGY}, volume = {13}, unique-id = {32850863}, issn = {1664-302X}, abstract = {Bacterial vaginosis (BV) is prevalent among women of reproductive age and has a high rate of recurrence, which can be largely attributed to ineffective BV biofilm eradication by current first-line antibiotics. In this study, we report that the Nile tilapia piscidin 4 (TP4) exhibits broad-spectrum antimicrobial and antibiofilm activity against BV-associated bacteria, but not beneficial lactobacilli. In addition, BV-associated Gardnerella vaginalis remains susceptible to TP4 even after continual exposure to the peptide for up to 22 passages. Gardnerella vaginalis and Streptococcus anginosus are both biofilm-forming BV-associated bacteria, and we found that combining TP4 peptide and disodium EDTA with the biofilm-disrupting agent, chitosan, can eradicate biofilms formed by single or mixed G. vaginalis and S. anginosus. In addition, long-term storage of TP4 peptide in chitosan did not diminish its bactericidal activity toward G. vaginalis. Preformulation studies were performed using High performance liquid chromatography (HPLC) and Circular Dichroism (CD). The long-term stability of TP4 peptide was assessed under various conditions, such as different temperatures and ionic strengths, and in the presence of H2O2 and lactic acid. When exposed to sodium dodecyl sulfate (SDS), TP4 maintained its secondary structure at various temperatures, salt and disodium EDTA concentrations. Furthermore, the TP4 microbicide formulation significantly reduced the colonization density of BV-associated bacteria in mice infected with single or mixed bacteria (G. vaginalis and S. anginosus). The TP4 microbicide formulation showed biocompatibility with beneficial human vaginal lactobacilli and female reproductive tissues in C57BL/6 mice. These results suggest that the TP4 microbicide formulation could be a promising topical microbicide agent for BV treatment. Copyright © 2022 Lin, Chen, Chuang and Chen.}, keywords = {Female; ARTICLE; MOUSE; CYTOTOXICITY; PROTEIN SECONDARY STRUCTURE; high performance liquid chromatography; nonhuman; animal tissue; animal model; animal experiment; toxicity testing; Gene Expression; scanning electron microscopy; hydrogen peroxide; drug formulation; minimum inhibitory concentration; immune response; Circular Dichroism; infrared spectroscopy; metronidazole; clindamycin; dodecyl sulfate sodium; ANTIMICROBIAL ACTIVITY; antibacterial activity; Biofilm; bacterial strain; bactericidal activity; virulence factor; Antibiotic resistance; biocompatibility; edetic acid; bacterial colonization; ionic strength; preformulation; methicillin resistant Staphylococcus aureus; vaginitis; cytokine response; edetate disodium; Bacterial vaginosis; vaginal lavage; broth dilution; vagina flora; polymicrobial biofilm; antibiofilm activity; Bacterial viability; resazurin assay; microtiter plate assay; trichomoniasis; AMPHIPATHIC ANTIMICROBIAL PEPTIDES; Nile tilapia piscidin 4; vaginal microbicide formulation}, year = {2022}, eissn = {1664-302X} } @article{MTMT:32850854, title = {Collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium}, url = {https://m2.mtmt.hu/api/publication/32850854}, author = {Li, Q. and Chen, S. and Zhu, K. and Huang, X. and Huang, Y. and Shen, Z. and Ding, S. and Gu, D. and Yang, Q. and Sun, H. and Hu, F. and Wang, H. and Cai, J. and Ma, B. and Zhang, R. and Shen, J.}, doi = {10.1038/s41467-022-29493-0}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {13}, unique-id = {32850854}, issn = {2041-1723}, abstract = {The acquisition of resistance to one antibiotic sometimes leads to collateral sensitivity to a second antibiotic. Here, we show that vancomycin resistance in Enterococcus faecium is associated with a remarkable increase in susceptibility to pleuromutilin antibiotics (such as lefamulin), which target the bacterial ribosome. The trade-off between vancomycin and pleuromutilins is mediated by epistasis between the van gene cluster and msrC, encoding an ABC-F protein that protects bacterial ribosomes from antibiotic targeting. In mouse models of vancomycin-resistant E. faecium colonization and septicemia, pleuromutilin treatment reduces colonization and improves survival more effectively than standard therapy (linezolid). Our findings suggest that pleuromutilins may be useful for the treatment of vancomycin-resistant E. faecium infections. © 2022, The Author(s).}, keywords = {COLONIZATION; Sensitivity analysis; antibiotics; TRADE-OFF}, year = {2022}, eissn = {2041-1723} } @article{MTMT:34136816, title = {Advance in collateral sensitivity in drug-resistant bacteria}, url = {https://m2.mtmt.hu/api/publication/34136816}, author = {Li, Qian and Zhu, Kui}, journal-iso = {WEISHENGWU XUEBAO / ACTA MICROBIOL SIN}, journal = {WEISHENGWU XUEBAO / ACTA MICROBIOLOGICA SINICA}, volume = {62}, unique-id = {34136816}, issn = {0001-6209}, year = {2022}, pages = {1688-1697} } @article{MTMT:32868163, title = {A novel antimicrobial peptide found in Pelophylax nigromaculatus}, url = {https://m2.mtmt.hu/api/publication/32868163}, author = {Lu, Chengyu and Liu, Lingling and Ma, Chengbang and Di, Liuqing and Chen, Tianbao}, doi = {10.1186/s43141-022-00366-9}, journal-iso = {J GENET ENG BIOTECH}, journal = {JOURNAL OF GENETIC ENGINEERING AND BIOTECHNOLOGY}, volume = {20}, unique-id = {32868163}, issn = {1687-157X}, abstract = {Background: Many active peptides have been found in frog skin secretions. In this paper, our research focused on Pelophylax nigromaculatus and found a broad-spectrum antimicrobial peptide Nigrocin-PN based on the molecular cloning technique. Thereafter, the "Rana box"function was briefly studied by two mutated peptides (Nigrocin-M1 and Nigrocin-M2). Furthermore, in vitro and in vivo assays were used to characterize the peptide's biofunctions, and the peptide's function in treating multidrug-resistant pathogens was also studied. Results: Nigrocin-PN not only displayed potent antimicrobial abilities in vitro but also significantly ameliorated pulmonary inflammation induced by Klebsiella pneumoniae in vivo. By comparing, leucine-substituted analogue Nigrocin-M1 only displayed bactericidal abilities towards gram-positive bacteria, while the shorter analogue Nigrocin-M2 lost this function. More strikingly, Nigrocin-PN exhibited synergistic effects with commonly used antibiotics; in vitro evolution experiments revealed that coadministration between Nigrocin-PN and ampicillin could delay Staphylococcus aureus antibiotic resistance acquisition. Kinetics and morphology studies indicate that antibacterial mechanisms involved membrane destruction. Furthermore, toxicities and anticancer abilities of these peptides were also studied; compared to two analogues, Nigrocin-PN showed mild haemolytic activity and indistinctive cytotoxicity towards normal cell lines HMEC-1 and HaCaT. Conclusions: A broad-spectrum antimicrobial peptide Nigrocin-PN was discovered from the skin secretion of Pelophylaxnigromaculatus. Structurally,"Rana box" played a crucial role in reducing toxicities without compromising antibacterial abilities, and Nigrocin-PN could be a desired therapeutic candidate.}, keywords = {MECHANISMS; RESISTANCE; Biotechnology & Applied Microbiology; Environmental Sciences; Thanatin; SECONDARY STRUCTURE ANALYSES}, year = {2022}, eissn = {2090-5920} } @book{MTMT:34075792, title = {Machine Learning for Drug Discovery}, url = {https://m2.mtmt.hu/api/publication/34075792}, isbn = {9780841299238}, author = {Melo, Marcelo C.R. and Maasch, Jacqueline R. M. A. and Fuente Nunez, Cesar de la}, doi = {10.1021/acsinfocus.7e5017}, publisher = {ACS}, unique-id = {34075792}, year = {2022}, orcid-numbers = {Melo, Marcelo C.R./0000-0001-6901-1646; Maasch, Jacqueline R. M. A./0000-0003-0432-3547; Fuente Nunez, Cesar de la/0000-0002-2005-5629} } @article{MTMT:33041605, title = {Fabricating effective heterojunction in metal-organic framework-derived self-cleanable and dark/visible-light dual mode antimicrobial CuO/AgX (X = Cl, Br, or I) nanocomposites}, url = {https://m2.mtmt.hu/api/publication/33041605}, author = {Midhu, Francis M. and Thakur, A. and Balapure, A. and Ray, Dutta J. and Ganesan, R.}, doi = {10.1016/j.cej.2022.137363}, journal-iso = {CHEM ENG J}, journal = {CHEMICAL ENGINEERING JOURNAL}, volume = {446}, unique-id = {33041605}, issn = {1385-8947}, abstract = {Owing to the alarming consequences of antimicrobial resistance, the requirements for effective antimicrobial materials working under dark and visible-light conditions are on the high rise. On a different note, heterojunctions between semiconductors are highly desirable to enhance the photocatalytic activity of the individual components in a synergistic way. In this work, we address these two aspects in a single material composition through a rationally designed synthetic strategy. Among several candidates, silver and copper are known to exhibit high antimicrobial characteristics in the dark. Besides, CuO and silver halides are known for their visible-light photocatalytic activity. Hence, a copper-based porous metal organic framework, Cu-BTC, has been deposited with a silver halide followed by calcination to yield CuO/AgX (X = Cl, Br, or I) nanocomposites. The initial deposition of the silver halide over the MOF is envisaged to provide a high dispersion of the halide in the CuO matrix through numerous anchoring pods and thereby result in a tight and effective heterojunction. The nanocomposites obtained through this approach have been characterized structurally and morphologically using various techniques. The nanocomposites have been studied for their visible-light photocatalytic and self-cleaning ability via photodegradation of methylene blue and 4-chlorophenol as model systems. Further, their antimicrobial efficacy has been studied against E. coli and S. aureus both under dark and visible-light conditions. In addition to revealing the high potential of the CuO/AgX nanocomposites towards environmental applications, the synthetic approach presented herein can potentially be extrapolated to fabricate exotic compositions possessing enhanced efficacy. © 2022 Elsevier B.V.}, keywords = {NANOCOMPOSITES; light; Escherichia coli; COPPER; Reactive oxygen species; Reactive oxygen species; Heterojunctions; Aromatic compounds; methylene blue; methylene blue; Photocatalysis; 4-CHLOROPHENOL; ANTIMICROBIAL RESISTANCE; Visible light; PHOTOCATALYTIC ACTIVITY; Dual modes; METAL-ORGANIC FRAMEWORKS; Light conditions; Copper oxides; Metalorganic frameworks (MOFs); Silver halides; antimicrobial materials; Antimicrobial resistances; Cu-BTC; Cu-BTC; Silver halide; 4-chlorophenols}, year = {2022}, eissn = {1873-3212} } @article{MTMT:33225790, title = {Tilted State Population of Antimicrobial Peptide PGLa Is Coupled to the Transmembrane Potential}, url = {https://m2.mtmt.hu/api/publication/33225790}, author = {Németh, Lukács and Martinek, Tamás and Jójárt, Balázs}, doi = {10.1021/acs.jcim.2c00667}, journal-iso = {J CHEM INF MODEL}, journal = {JOURNAL OF CHEMICAL INFORMATION AND MODELING}, volume = {62}, unique-id = {33225790}, issn = {1549-9596}, year = {2022}, eissn = {1549-960X}, pages = {4963-4969}, orcid-numbers = {Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:32850815, title = {A Novel Proline-Rich Cathelicidin from the Alpaca Vicugna pacos with Potency to Combat Antibiotic-Resistant Bacteria: Mechanism of Action and the Functional Role of the C-Terminal Region}, url = {https://m2.mtmt.hu/api/publication/32850815}, author = {Panteleev, P.V. and Safronova, V.N. and Kruglikov, R.N. and Bolosov, I.A. and Bogdanov, I.V. and Ovchinnikova, T.V.}, doi = {10.3390/membranes12050515}, journal-iso = {MEMBRANES-BASEL}, journal = {MEMBRANES (BASEL)}, volume = {12}, unique-id = {32850815}, abstract = {Over recent years, a growing number of bacterial species have become resistant to clinically relevant antibiotics. Proline-rich antimicrobial peptides (PrAMPs) having a potent antimicrobial activity and a negligible toxicity toward mammalian cells attract attention as new templates for the development of antibiotic drugs. Here, we mined genomes of all living Camelidae species and found a novel family of Bac7-like proline-rich cathelicidins which inhibited bacterial protein synthesis. The N-terminal region of a novel peptide from the alpaca Vicugna pacos named VicBac is responsible for inhibition of bacterial protein synthesis with an IC50 value of 0.5 µM in the E. coli cell-free system whereas the C-terminal region allows the peptide to penetrate bacterial membranes effectively. We also found that the full-length VicBac did not induce bacterial resistance after a two-week selection experiment, unlike the N-terminal truncated analog, which depended on the SbmA transport system. Both pro-and anti-inflammatory action of VicBac and its N-terminal truncated variant on various human cell types was found by multiplex immunoassay. The presence of the C-terminal tail in the natural VicBac does not provide for specific immune-modulatory effects in vitro but enhances the observed impact compared with the truncated analog. The pronounced antibacterial activity of VicBac, along with its moderate adverse effects on mammalian cells, make this molecule a promising scaffold for the development of peptide antibiotics. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.}, keywords = {PEPTIDES; CELLS; Escherichia coli; Cytology; biosynthesis; antibiotics; MAMMALS; bacterial protein; Antimicrobial peptide; Antimicrobial peptide; Scaffolds (biology); cathelicidin; cathelicidin; Mammalian cells; PROLINE-RICH PEPTIDE; PROLINE-RICH PEPTIDE; Bacterial resistance; Bacterial resistance; C-terminal regions; translation inhibitor; translation inhibitor; N-terminals; SbmA transporter; SbmA transporter}, year = {2022}, eissn = {2077-0375} } @article{MTMT:34770476, title = {Antibiofilm Effects of Bacteriocin BMP32r on Listeria monocytogenes}, url = {https://m2.mtmt.hu/api/publication/34770476}, author = {Qiao, Zhu and Zhang, Leshan and Wang, Xin and Liu, Bianfang and Shan, Yuanyuan and Yi, Yanglei and Zhou, Yuan and Lu, Xin}, doi = {10.1007/s12602-021-09863-8}, journal-iso = {PROBIOTICS ANTIMICROB PROTEINS}, journal = {PROBIOTICS AND ANTIMICROBIAL PROTEINS}, volume = {14}, unique-id = {34770476}, issn = {1867-1306}, abstract = {Listeria monocytogenes is a well-known foodborne pathogen that usually lives as biofilm to cope with unfavorable surroundings. Bacteriocins have been reported as antimicrobial compounds, and their bactericidal actions have been extensively studied, but their antibiofilm actions have rarely been studied. Previous study indicated that bacteriocin BMP32r has a broad-spectrum antibacterial activity. In this study, the efficacy of BMP32r against the planktonic bacteria, inhibition of forming biofilm, destruction of mature biofilm, and kill persisters of L. monocytogenes ATCC 15,313 was determined. BMP32r exhibited the bactericidal effect on L. monocytogenes planktonic bacteria. Crystal violet staining showed that sub-minimum inhibitory concentrations (SICs) of BMP32r (1/32 x MIC and 1/16 x MIC) significantly (p < 0.001) inhibit the biofilm formation. In addition, the results of CCK-8, plate count, ruthenium red staining, scanning electron microscopy, and real-time quantitative PCR assay showed that SICs of BMP32r reduced cell adhesion, exopolysaccharide production, quorum sensing, and virulence genes expression in biofilm formation. Moreover, higher concentrations of BMP32r (2 x MIC and 4 x MIC) disrupt the mature biofilm by killing the bacteria in the biofilm and kill L. monocytogenes persisters bacteria effectively. Therefore, BMP32r has promising potential as an antibiofilm agent to combat L. monocytogenes.}, keywords = {MECHANISM; COMBINATION; ANTIBACTERIAL; Virulence; PLANKTONIC BACTERIA; Biofilm; Biofilm formation; STRATEGIES; persistence; bacteriocin; Biotechnology & Applied Microbiology; nisin; adhesion}, year = {2022}, eissn = {1867-1314}, pages = {1067-1076}, orcid-numbers = {Qiao, Zhu/0000-0001-8588-3989; Wang, Xin/0000-0001-8891-8868} } @article{MTMT:33597301, title = {Cloning and expression of two anti-lipopolysaccharide factors in Eriocheir hepuensis under Vibrio alginolyticus-induced stress}, url = {https://m2.mtmt.hu/api/publication/33597301}, author = {Ren, T. and Liu, J. and Liu, K. and Zhang, Z. and Ma, Z. and Dan, S.F. and Lan, Z. and Lu, M. and Fang, H. and Zhang, Y. and Zhu, P. and Liao, Y.}, doi = {10.1111/jfb.15261}, journal-iso = {J FISH BIOL}, journal = {JOURNAL OF FISH BIOLOGY}, unique-id = {33597301}, issn = {0022-1112}, abstract = {Anti-lipopolysaccharide factors (ALFs) are small basic proteins that exhibit broad-spectrum antiviral properties and antibacterial activity. In this research, we cloned and studied two Eriocheir hepuensis ALFs, EhALF2 and EhALF3. The results showed that the open reading frame lengths of EhALF2 and EhALF3 were 363 and 372 bp, encoding 120 and 123 amino acids, respectively. Their sequences both contained an Lipopolysaccharide-binding (LPS) domain and were highly similarity to other crab ALFs. qRT–PCR showed that EhALF2 and EhALF3 were detected in nine examined tissues and were expressed the highest in the haemocytes. After challenge with Vibrio alginolyticus, in the hepatopancreas, the expression levels of EhALF2 and EhALF3 reached the highest levels at 48 and 3 h, respectively. In the heart, the expression levels of the two genes were highest at 12 h. These results indicate that EhALF2 and EhALF3 could participate in the resistance of E. hepuensis to V. alginolyticus stress within a short time. They have potential applications in the study of environmental stress markers and disease-resistance factors in E. hepuensis. © 2022 Fisheries Society of the British Isles.}, keywords = {EXPRESSION; Vibrio alginolyticus; EhALF2; EhALF3; Eriocheir hepuensis}, year = {2022}, eissn = {1095-8649} } @article{MTMT:33551123, title = {The future of recombinant host defense peptides}, url = {https://m2.mtmt.hu/api/publication/33551123}, author = {Roca-Pinilla, R. and Lisowski, L. and Arís, A. and Garcia-Fruitós, E.}, doi = {10.1186/s12934-022-01991-2}, journal-iso = {MICROB CELL FACT}, journal = {MICROBIAL CELL FACTORIES}, volume = {21}, unique-id = {33551123}, issn = {1475-2859}, abstract = {The antimicrobial resistance crisis calls for the discovery and production of new antimicrobials. Host defense peptides (HDPs) are small proteins with potent antibacterial and immunomodulatory activities that are attractive for translational applications, with several already under clinical trials. Traditionally, antimicrobial peptides have been produced by chemical synthesis, which is expensive and requires the use of toxic reagents, hindering the large-scale development of HDPs. Alternatively, HDPs can be produced recombinantly to overcome these limitations. Their antimicrobial nature, however, can make them toxic to the hosts of recombinant production. In this review we explore the different strategies that are used to fine-tune their activities, bioengineer them, and optimize the recombinant production of HDPs in various cell factories. © 2022, The Author(s).}, keywords = {metabolism; GENETICS; review; human; protein analysis; innate immunity; defensin; Cell Fusion; Inclusion Bodies; nonhuman; Solubility; unclassified drug; encapsulation; recombinant protein; protein synthesis; Immunity, Innate; antiinfective agent; protein domain; process optimization; anti-bacterial agents; Antibiotic resistance; drug synthesis; drug activity; host cell; drug research; Anti-Infective Agents; yeast cell; cell inclusion; ANTIMICROBIAL RESISTANCE; polypeptide antibiotic agent; bacterial cell; insect cell; APIDAECIN; Bioengineering; Antimicrobial Cationic Peptides; Melittin; puroindoline a; Synergistic effect; antimicrobial cationic peptide; indolicidin; Piscidin; sericin; Host defense peptides; Thanatin; Human beta defensin 1; RECOMBINANT PRODUCTION; antimicrobial proteins; fungal cell; Pexiganan; Tritrpticin; gloverin; human beta defensin 2; Javanicin; human neutrophil peptide 1; bovine lingual antimicrobial peptide; buforin ii; cathelicidin bf; cryptidin 2; fowlicidin 1; fungal defensin like peptide; human alpha defensin 5; human beta defensin 118; human beta defensin 3; human beta defensin 4; human beta defensin 6; human beta defensin defb136; hybrid peptide cecropin ad; innate defense regulator 1; insect defensin a; lactoferrampin b; plectasin; scorpine; snakin 1}, year = {2022}, eissn = {1475-2859} } @article{MTMT:33087038, title = {Rational Discovery of Antimicrobial Peptides by Means of Artificial Intelligence}, url = {https://m2.mtmt.hu/api/publication/33087038}, author = {Ruiz, Puentes P. and Henao, M.C. and Cifuentes, J. and Muñoz-Camargo, C. and Reyes, L.H. and Cruz, J.C. and Arbeláez, P.}, doi = {10.3390/membranes12070708}, journal-iso = {MEMBRANES-BASEL}, journal = {MEMBRANES (BASEL)}, volume = {12}, unique-id = {33087038}, abstract = {Antibiotic resistance is a worldwide public health problem due to the costs and mortality rates it generates. However, the large pharmaceutical industries have stopped searching for new antibiotics because of their low profitability, given the rapid replacement rates imposed by the increasingly observed resistance acquired by microorganisms. Alternatively, antimicrobial peptides (AMPs) have emerged as potent molecules with a much lower rate of resistance generation. The discovery of these peptides is carried out through extensive in vitro screenings of either rational or non-rational libraries. These processes are tedious and expensive and generate only a few AMP candidates, most of which fail to show the required activity and physicochemical properties for practical applications. This work proposes implementing an artificial intelligence algorithm to reduce the required experimentation and increase the efficiency of high-activity AMP discovery. Our deep learning (DL) model, called AMPs-Net, outperforms the state-of-the-art method by 8.8% in average precision. Furthermore, it is highly accurate to predict the antibacterial and antiviral capacity of a large number of AMPs. Our search led to identifying two unreported antimicrobial motifs and two novel antimicrobial peptides related to them. Moreover, by coupling DL with molecular dynamics (MD) simulations, we were able to find a multifunctional peptide with promising therapeutic effects. Our work validates our previously proposed pipeline for a more efficient rational discovery of novel AMPs. © 2022 by the authors.}, keywords = {PEPTIDES; PEPTIDES; IN-VITRO; PHYSICOCHEMICAL PROPERTIES; Artificial intelligence; GRAPHS; MICROORGANISMS; antibiotics; molecular dynamics; molecular dynamics; GRAPH; Antimicrobial; Antimicrobial; pharmaceutical industry; Low rates; Antimicrobial peptide; mortality rate; Deep learning; antibiotics resistance; Cost rates; Replacement rates}, year = {2022}, eissn = {2077-0375} } @article{MTMT:32850864, title = {Combination of Amphiphilic Cyclic Peptide [R4W4] and Levofloxacin against Multidrug-Resistant Bacteria}, url = {https://m2.mtmt.hu/api/publication/32850864}, author = {Sajid, M.I. and Lohan, S. and Kato, S. and Tiwari, R.K.}, doi = {10.3390/antibiotics11030416}, journal-iso = {ANTIBIOTICS-BASEL}, journal = {ANTIBIOTICS}, volume = {11}, unique-id = {32850864}, abstract = {Bacterial resistance is a growing global concern necessitating the discovery and development of antibiotics effective against the drug-resistant bacterial strain. Previously, we reported a cyclic antimicrobial peptide [R4W4] containing arginine (R) and tryptophan (W) with a MIC of 2.67 µg/mL (1.95 µM) against methicillin-resistant Staphylococcus aureus (MRSA). Herein, we investigated the cyclic peptides [R4W4] or linear (R4W4) and their conjugates (covalent or noncovalent) with levofloxacin (Levo) with the intent to improve their potency to target drug-resistant bacteria. The physical mixture of the Levo with the cyclic [R4W4] proved to be significantly effective against all strains of bacteria used in the study as compared to covalent conjugation. Furthermore, the checkerboard assay revealed the significant synergistic effect of the peptides against all studied strains except for the wild type S. aureus, in which the partial synergy was observed. The hemolysis assay revealed less cytotoxicity of the physical mixture of the Levo with [R4W4] (22%) as compared to [R4W4] alone (80%). The linear peptide (R4W4) and the cyclic [R4W4] demonstrated ~90% and 85% cell viability at 300 µg/mL in the triple-negative breast cancer cells (MDA-MB-231) and the normal kidney cells (HEK-293), respectively. Similar trends were also observed in the cell viability of Levo-conjugates on these cell lines. Furthermore, the time-kill kinetic study of the combination of [R4W4] and Levo demonstrate rapid killing action at 4 h for MRSA (ATCC BAA-1556) and 12 h for E. coli (ATCC BAA-2452), P. aeruginosa (ATCC BAA-1744), and K. pneumoniae (ATCC BAA-1705). These results provide the effectiveness of a combination of Levo with cyclic [R4W4] peptide, which may provide an opportunity to solve the intriguing puzzle of treating bacterial resistance. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.}, keywords = {ARTICLE; CONJUGATE; human; arginine; Escherichia coli; controlled study; nonhuman; cell proliferation; human cell; unclassified drug; minimum inhibitory concentration; tryptophan; PEPTIDE SYNTHESIS; antibacterial activity; Pseudomonas aeruginosa; Cell viability; bactericidal activity; Antibiotic resistance; levofloxacin; reversed phase high performance liquid chromatography; cyclopeptide; colony forming unit; matrix assisted laser desorption ionization time of flight mass spectrometry; methicillin resistant Staphylococcus aureus; combination therapy; klebsiella pneumoniae; Synergistic effect; matrix-assisted laser desorption-ionization mass spectrometry; MTS assay; cytotoxicity assay; Drug-resistant bacteria; cyclic antimicrobial peptides; Checkerboard assay; Antibacterial resistance; hemolysis assay; multidrug resistant bacterium; fractional inhibitory concentration; cyclopeptide [R4W4]}, year = {2022}, eissn = {2079-6382} } @article{MTMT:33268479, title = {Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy}, url = {https://m2.mtmt.hu/api/publication/33268479}, author = {Sandin, Daniel and Valle, Javier and Morata, Jordi and Andreu, David and Torrent, Marc}, doi = {10.3390/pharmaceutics14102169}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {14}, unique-id = {33268479}, issn = {1999-4923}, abstract = {Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of Escherichia coli with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant vis-a-vis the eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments.}, keywords = {MECHANISM; TOLERANCE; ANTIMICROBIAL PEPTIDES; Polymyxin B; antibiotic tolerance; pleurocidin; ANTIMICROBIAL PEPTIDE LL-37}, year = {2022}, eissn = {1999-4923} } @mastersthesis{MTMT:34075946, title = {Design and optimization of new antimicrobial peptides against gram-negative bacteria}, url = {https://m2.mtmt.hu/api/publication/34075946}, author = {Sandin García, Daniel}, unique-id = {34075946}, year = {2022} } @article{MTMT:33181883, title = {Benchmarks in antimicrobial peptide prediction are biased due to the selection of negative data}, url = {https://m2.mtmt.hu/api/publication/33181883}, author = {Sidorczuk, Katarzyna and Gagat, Przemyslaw and Pietluch, Filip and Kala, Jakub and Rafacz, Dominik and Bakala, Laura and Slowik, Jadwiga and Kolenda, Rafal and Rodiger, Stefan and Fingerhut, Legana C. H. W. and Cooke, Ira R. and Mackiewicz, Pawel and Burdukiewicz, Michal}, doi = {10.1093/bib/bbac343}, journal-iso = {BRIEF BIOINFORM}, journal = {BRIEFINGS IN BIOINFORMATICS}, unique-id = {33181883}, issn = {1467-5463}, abstract = {Antimicrobial peptides (AMPs) are a heterogeneous group of short polypeptides that target not only microorganisms but also viruses and cancer cells. Due to their lower selection for resistance compared with traditional antibiotics, AMPs have been attracting the ever-growing attention from researchers, including bioinformaticians. Machine learning represents the most cost-effective method for novel AMP discovery and consequently many computational tools for AMP prediction have been recently developed. In this article, we investigate the impact of negative data sampling on model performance and benchmarking. We generated 660 predictive models using 12 machine learning architectures, a single positive data set and 11 negative data sampling methods; the architectures and methods were defined on the basis of published AMP prediction software. Our results clearly indicate that similar training and benchmark data set, i.e. produced by the same or a similar negative data sampling method, positively affect model performance. Consequently, all the benchmark analyses that have been performed for AMP prediction models are significantly biased and, moreover, we do not know which model is the most accurate. To provide researchers with reliable information about the performance of AMP predictors, we also created a web server AMPBenchmark for fair model benchmarking. AMP Benchmark is available at http://BioGenies.info/AMPBenchmark.}, keywords = {PREDICTION; machine learning; reproducibility; ANTIMICROBIAL PEPTIDES; Benchmarks; Negative sampling}, year = {2022}, eissn = {1477-4054}, orcid-numbers = {Sidorczuk, Katarzyna/0000-0001-6576-9054; Pietluch, Filip/0000-0001-6218-9804; Kala, Jakub/0000-0002-7187-6988; Rafacz, Dominik/0000-0003-0925-1909; Bakala, Laura/0000-0002-3213-2484; Slowik, Jadwiga/0000-0003-3466-8933; Kolenda, Rafal/0000-0002-8145-579X} } @article{MTMT:32850827, title = {NMR Structure and Localization of the Host Defense Peptide ThanatinM21F in Zwitterionic Dodecylphosphocholine Micelle: Implications in Antimicrobial and Hemolytic Activity}, url = {https://m2.mtmt.hu/api/publication/32850827}, author = {Sinha, S. and Bhattacharjya, S.}, doi = {10.1007/s00232-022-00223-3}, journal-iso = {J MEMBRANE BIOL}, journal = {JOURNAL OF MEMBRANE BIOLOGY}, unique-id = {32850827}, issn = {0022-2631}, abstract = {Non-hemolytic antimicrobial peptides (AMPs) are vital lead molecules for the designing and development of peptide-based antibiotics. Thanatin a 21-amino acid long single disulfide bonded AMP is known to be highly non-hemolytic with a limited toxicity to human cells and model animals. Thanatin demonstrates a potent antibacterial activity against multidrug-resistant Gram-negative pathogens. A single mutated variant of thanatin replaced last residue Met21 to Phe or thanatin M21F has recently been found to be more active compared to the native peptide. In order to gain mechanistic insights toward bacterial cell lysis versus non-hemolysis, here, we report atomic resolution structure and mode insertion of thanatinM21F reconstituted into zwitterionic detergent micelle by use of solution NMR spectroscopy. The 3D structure of thanatinM21F in DPC micelle is defined by an anti-parallel β-sheet between residues I9-F21 with a central cationic loop, residues N12-R14. PRE NMR studies revealed hydrophobic core residues of thanatinM21F are deeply inserted in the DPC micelle, while residues at the extended N-terminal half of the peptide are appeared to be mostly surface localized. Marked structural differences of thanatin and thanatinM21F in negatively charged LPS and DPC micelle could be correlated with non-hemolytic and antibacterial activity. Graphic Abstract: [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.}, keywords = {NMR; structure; Antimicrobial peptide; Thanatin; Host defense antimicrobial peptide; DPC micelle}, year = {2022}, eissn = {1432-1424} } @article{MTMT:33006776, title = {Evolutionary Instability of Collateral Susceptibility Networks in Ciprofloxacin-Resistant Clinical Escherichia coli Strains}, url = {https://m2.mtmt.hu/api/publication/33006776}, author = {Sorum, Vidar and Oynes, Emma L. and Moller, Anna S. and Harms, Klaus and Samuelsen, Orjan and Podnecky, Nicole L. and Johnsen, Pal J.}, doi = {10.1128/mbio.00441-22}, journal-iso = {MBIO}, journal = {MBIO}, volume = {13}, unique-id = {33006776}, issn = {2161-2129}, abstract = {Collateral sensitivity and resistance occur when resistance development toward one antimicrobial either potentiates or deteriorates the effect of others. Previous reports on collateral effects on susceptibility focus on newly acquired resistance determinants and propose that novel treatment guidelines informed by collateral networks may reduce the evolution, selection, and spread of antimicrobial resistance. In this study, we investigate the evolutionary stability of collateral networks in five ciprofloxacin-resistant, clinical Escherichia coli strains. After 300 generations of experimental evolution without antimicrobials, we show complete fitness restoration in four of five genetic backgrounds and demonstrate evolutionary instability in collateral networks of newly acquired resistance determinants. We show that compensatory mutations reducing efflux expression are the main drivers destabilizing initial collateral networks and identify rpoS as a putative target for compensatory evolution. Our results add another layer of complexity to future predictions and clinical application of collateral networks. IMPORTANCE Antimicrobial resistance occurs due to genetic alterations that affect different processes in bacteria. Thus, developing resistance toward one antimicrobial drug may also alter the response toward others (collateral effects). Understanding the mechanisms of such collateral effects may provide clinicians with a framework for informed antimicrobial treatment strategies, limiting the emergence of antimicrobial resistance. However, for clinical implementation, it is important that the collateral effects of resistance development are repeatable and temporarily stable. Here, we show that collateral effects caused by resistance development toward ciprofloxacin in clinical Escherichia coli strains are not temporarily stable because of compensatory mutations restoring the fitness burden of the initial resistance mutations. Consequently, this instability is complicating the general applicability and clinical implementation of collateral effects into treatment strategies.Antimicrobial resistance occurs due to genetic alterations that affect different processes in bacteria. Thus, developing resistance toward one antimicrobial drug may also alter the response toward others (collateral effects).}, keywords = {Escherichia coli; ciprofloxacin; COLLATERAL SENSITIVITY; ANTIMICROBIAL RESISTANCE; compensatory mutations}, year = {2022}, eissn = {2150-7511} } @article{MTMT:32850858, title = {A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function}, url = {https://m2.mtmt.hu/api/publication/32850858}, author = {Sun, C.-Q. and Peng, J. and Yang, L.-B. and Jiao, Z.-L. and Zhou, L.-X. and Tao, R.-Y. and Zhu, L.-J. and Tian, Z.-Q. and Huang, M.-J. and Guo, G.}, doi = {10.3389/fmicb.2022.872322}, journal-iso = {FRONT MICROBIOL}, journal = {FRONTIERS IN MICROBIOLOGY}, volume = {13}, unique-id = {32850858}, issn = {1664-302X}, abstract = {Global burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence and mortality in immunocompromised patients. Antimicrobial peptides (AMPs), in this context, represent promising alternatives having potential to be exploited for improving human health. In our previous studies, a Cecropin-4-derived peptide named C18 was found to possess a broader antibacterial spectrum after modification and exhibit significant antifungal activity against C. albicans. In this study, C18 shows antifungal activity against C. albicans or non-albicans Candida species with a minimum inhibitory concentration (MIC) at 4∼32 μg/ml, and clinical isolates of fluconazole (FLZ)-resistance C. tropicalis were highly susceptible to C18 with MIC value of 8 or 16 μg/ml. Additionally, C18 is superior to FLZ for killing planktonic C. albicans from inhibitory and killing kinetic curves. Moreover, C18 could attenuate the virulence of C. albicans, which includes damaging the cell structure, retarding hyphae transition, and inhibiting biofilm formation. Intriguingly, in the Galleria mellonella model with C. albicans infection, C18 could improve the survival rate of G. mellonella larvae to 70% and reduce C. albicans load from 5.01 × 107 to 5.62 × 104 CFU. For mechanistic action of C18, the level of reactive oxygen species (ROS) generation and cytosolic Ca2 + increased in the presence of C18, which is closely associated with mitochondrial dysfunction. Meanwhile, mitochondrial membrane potential (△Ψm) loss and ATP depletion of C. albicans occurred with the treatment of C18. We hypothesized that C18 might inhibit C. albicans via triggering mitochondrial dysfunction driven by ROS generation and Ca2 + accumulation. Our observation provides a basis for future research to explore the antifungal strategies and presents C18 as an attractive therapeutic candidate to be developed to treat candidiasis. Copyright © 2022 Sun, Peng, Yang, Jiao, Zhou, Tao, Zhu, Tian, Huang and Guo.}, keywords = {mitochondrial dysfunction; Antifungal activity; Candida albicans; ROS; G. mellonella; cecropin-4 derived peptide}, year = {2022}, eissn = {1664-302X} } @article{MTMT:33041606, title = {In pursuit of next-generation therapeutics: Antimicrobial peptides against superbugs, their sources, mechanism of action, nanotechnology-based delivery, and clinical applications}, url = {https://m2.mtmt.hu/api/publication/33041606}, author = {Thakur, A. and Sharma, A. and Alajangi, H.K. and Jaiswal, P.K. and Lim, Y.-B. and Singh, G. and Barnwal, R.P.}, doi = {10.1016/j.ijbiomac.2022.07.103}, journal-iso = {INT J BIOL MACROMOL}, journal = {INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES}, volume = {218}, unique-id = {33041606}, issn = {0141-8130}, abstract = {Antimicrobial peptides (AMPs) attracted attention as potential source of novel antimicrobials. Multi-drug resistant (MDR) infections have emerged as a global threat to public health in recent years. Furthermore, due to rapid emergence of new diseases, there is pressing need for development of efficient antimicrobials. AMPs are essential part of the innate immunity in most living organisms, acting as the primary line of defense against foreign invasions. AMPs kill a wide range of microorganisms by primarily targeting cell membranes or intracellular components through a variety of ways. AMPs can be broadly categorized based on their physico-chemical properties, structure, function, target and source of origin. The synthetic analogues produced either with suitable chemical modifications or with the use of suitable delivery systems are projected to eliminate the constraints of toxicity and poor stability commonly linked with natural AMPs. The concept of peptidomimetics is gaining ground around the world nowadays. Among the delivery systems, nanoparticles are emerging as potential delivery tools for AMPs, amplifying their utility against a variety of pathogens. In the present review, the broad classification of various AMPs, their mechanism of action (MOA), challenges associated with AMPs, current applications, and novel strategies to overcome the limitations have been discussed. © 2022}, keywords = {ANTIMICROBIAL PEPTIDES; ANTIMICROBIAL RESISTANCE; Bacteriocins; Mammalian AMPs; Marine AMPs; Plant AMPs}, year = {2022}, eissn = {1879-0003}, pages = {135-156} } @article{MTMT:32636175, title = {Analysis of microbial community resistance mechanisms in groundwater contaminated with SAs and high NH4+-Fe-Mn}, url = {https://m2.mtmt.hu/api/publication/32636175}, author = {Wang, J. and Zhang, Y. and Ding, Y. and Song, H. and Liu, T.}, doi = {10.1016/j.scitotenv.2022.153036}, journal-iso = {SCI TOTAL ENVIRON}, journal = {SCIENCE OF THE TOTAL ENVIRONMENT}, volume = {817}, unique-id = {32636175}, issn = {0048-9697}, abstract = {The resistance mechanism of microbial communities in contaminated groundwater under the combined stress of sulfonamide antibiotics (SAs), NH4+, and Fe-Mn exceeding the standard levels was studied in an agricultural area along the Songhua River in Northeast China with developed livestock and poultry breeding. Representative points were selected in the study area to explore the response of environmental parameters and microbial communities, and microscopic experiments with different SA concentrations were conducted with background groundwater. The results showed a complex relationship between microbial communities and environmental factors. The environmental factors SM, SM2, SMX, DOC, NO3−, Fe, Mn, and HCO3− significantly affected the microbial community, with SMX, DOC, and Mn having the greatest effect. Three types of antibiotics with similar properties had different effects on the microbial community, and these effects were not simply additive or superimposed. After adding SAs, Proteobacteria with multi-resistance (99.85%) became the dominant phylum, and Acinetobacter (98.68%) became the dominant genus with SA resistance. SAs have a significant influence on bacterial chemotaxis, transporters, substance transport, and metabolism. Microorganisms resist the influence of SAs via a series of resistance mechanisms, such as enhancing the synthesis of relevant enzymes, generating new biochemical reactions, and reducing the transport of harmful substances through cell membranes. We also found that the proportion of exogenous compound degradation and metabolism-related functional genes in the presence of high SA concentrations increased significantly, which may be related to the degradation of SAs by microorganisms. © 2022 Elsevier B.V.}, keywords = {PH; metabolism; calcium; ARTICLE; SODIUM; POTASSIUM; SULFUR COMPOUNDS; nitrate; AMMONIA; Breeding; controlled study; MAGNESIUM; Cell Membrane; Cytology; nonhuman; Binary alloys; IRON; Manganese; CHINA; CHINA; SULFATE; MICROORGANISMS; NITRITE; quality control; POULTRY; BIODEGRADATION; BIODEGRADATION; AGRICULTURE; physical chemistry; antibiotics; antibiotics; CHLORIDE; Chemotaxis; environmental factor; population abundance; GROUNDWATER; GROUNDWATER; GROUNDWATER; MICROBIAL DIVERSITY; microbial communities; MICROBIAL COMMUNITY; MICROBIAL COMMUNITY; MICROBIAL COMMUNITY; PROTEOBACTERIA; acinetobacter; BICARBONATE; BIOCHEMISTRY; aminoglycoside antibiotic agent; beta lactamase; penicillin derivative; cephalosporin; Antibiotic resistance; Antibiotic resistance; sulfonamide; chloramphenicol; Chemical oxygen demand; water quality; concentration (composition); Dissolved oxygen; DNA content; environmental factors; bacterial DNA; RNA sequence; enzyme synthesis; Iron alloys; Groundwater pollution; Groundwater pollution; water contamination; ground water; aerobic bacterium; Firmicutes; RNA 16S; agricultural emission; Agricultural areas; LIVESTOCK; Metagenomics; Metagenomics; Contaminated groundwater; protein histidine kinase; SONGHUA RIVER; resistance mechanisms; Resistance mechanism; Sulfonamide antibiotics; concentration (parameter); combined stress; Antibiotic concentration; Sulfonamide antibiotics (SAs); Sulphonamide antibiotic}, year = {2022}, eissn = {1879-1026} } @article{MTMT:32636192, title = {β-Cyclodextrin-Derivative-Functionalized Graphene Oxide/Graphitic Carbon Nitride Composites with a Synergistic Effect for Rapid and Efficient Sterilization}, url = {https://m2.mtmt.hu/api/publication/32636192}, author = {Wang, T. and Bai, Z. and Wei, W. and Hou, F. and Guo, W. and Wei, A.}, doi = {10.1021/acsami.1c24047}, journal-iso = {ACS APPL MATER INTER}, journal = {ACS APPLIED MATERIALS & INTERFACES}, volume = {14}, unique-id = {32636192}, issn = {1944-8244}, abstract = {The nonselectivity of phototherapy and the hydrophobicity of phototherapy agents limit their application in the treatment of antibiotic-resistant bacteria. In this work, β-cyclodextrin-derivative-functionalized graphene oxide (GO)/graphitic carbon nitride (g-C3N4) antibacterial materials (CDM/GO/CN) were designed and synthesized. CN is used as a photosensitizer for photodynamic therapy (PDT) and GO as a photothermal agent for photothermal therapy (PTT). In addition, the supramolecular host-guest complex on the substrate can not only increase the inherent water solubility of the substrate and reduce the aggregation of the photosensitizer/photothermal agent but also manipulate the interaction between the photosensitizer/photothermal agent and bacteria to capture specific bacteria. The hyperthermia caused by PTT denatures proteins on the cell membrane, allowing reactive oxygen species (ROS) to enter the cell better and kill bacteria. The specific capture of Escherichia coli CICC 20091 by mannose significantly improves the sterilization efficiency and reduces side effects. The synergistic antibacterial agent shows excellent antibacterial efficacy of over 99.25% against E. coli CICC 20091 after 10 min of 635 + 808 nm dual-light irradiation. Moreover, cell proliferation experiments show that the composite material has good biocompatibility, expected to have applications in bacterial infections. ©}, keywords = {PHYSICOCHEMICAL PROPERTIES; Escherichia coli; cell proliferation; Graphene; CYCLODEXTRINS; supramolecular chemistry; ANTIBACTERIALS; Carbon nitride; photodynamic therapy; photodynamic therapy; biocompatibility; PHOTOSENSITIZERS; Cyclodextrin derivatives; PHOTOTHERMAL THERAPY; PHOTOTHERMAL THERAPY; Antimicrobial agents; Photo-thermal; Bioactives; Photosensitiser; Graphitic carbon nitrides; Specific capture; Specific capture; Synergistic antibacterial; Synergistic antibacterial; Sterilization (cleaning); supramolecular bioactive complex; supramolecular bioactive complex}, year = {2022}, eissn = {1944-8252}, pages = {474-483} } @article{MTMT:33041607, title = {Novel functionalized selenium nanowires as antibiotic adjuvants in multiple ways to overcome drug resistance of multidrug-resistant bacteria}, url = {https://m2.mtmt.hu/api/publication/33041607}, author = {Wang, Z. and Yin, C. and Gao, Y. and Liao, Z. and Li, Y. and Wang, W. and Sun, D.}, doi = {10.1016/j.bioadv.2022.212815}, journal-iso = {BIOMATER ADV}, journal = {BIOMATERIALS ADVANCES}, volume = {137}, unique-id = {33041607}, issn = {2772-9516}, abstract = {Methicillin-resistant Staphylococcus (MRS) is a multi-drug resistant bacteria that pose a serious threat to human health. Antibacterial nanomaterials are becoming a promising antibiotic substitute or antibiotic adjuvants. In this work, selenium nanowires were modified with nano‑silver (Ag NPs) with antibacterial activity and [Ru(bpy)2dppz]2+ with fluorescent labeling of DNA (SRA), and the antibacterial activity, antibacterial mechanism and biological toxicity of SRA synergistic antibiotics were studied. In vitro, antibacterial results show that SRA (12 μg/mL) improves the antibacterial activity of various antibiotics against resistant bacteria and significantly slows the development of bacterial resistance to antibiotics. Studies on antibacterial mechanisms have shown that SRA synergistic antibiotics destroy drug-resistant bacteria through a combination of physical (physical damage) and chemical pathways (destruction of biofilm, membrane depolarization, cell membrane destruction, adenosine triphosphate consumption and reactive oxygen species production). Transcriptomics analysis found that SRA affects bacterial activity by affecting bacterial biosynthesis, ATP synthesis and biofilm formation. Furthermore, SRA synergistic antibiotics can accelerate wound healing of bacterial infection by reducing the inflammatory response. The toxicity evaluation results show that SRA has extremely low cellular and in vivo toxicity. SRA has the potential of clinical application as multiple antibiotic adjuvants to deal with resistant bacterial infections. © 2022 Elsevier B.V.}, keywords = {BACTERIA; Cytology; TOXICITY; NANOWIRES; nanostructured materials; Selenium; antibiotics; DRUG-RESISTANCE; nanomaterials; ANTIBACTERIALS; BIOFILMS; Biofilm; BIOCHEMISTRY; Bacterial Infections; Antibiotic resistance; Functionalized; Health risks; Adenosinetriphosphate; Anti-bacterial activity; resistant bacteria; Drug-resistant bacteria; antibiotics resistance; antibacterial mechanism; Antibiotic adjuvant; Antibiotic adjuvant; antibacterial mechanisms}, year = {2022}, eissn = {2772-9508} } @article{MTMT:32850862, title = {Breaking the Rebellion: Photodynamic Inactivation against Erwinia amylovora Resistant to Streptomycin}, url = {https://m2.mtmt.hu/api/publication/32850862}, author = {Wimmer, A. and Glueck, M. and Ckurshumova, W. and Liu, J. and Fefer, M. and Plaetzer, K.}, doi = {10.3390/antibiotics11050544}, journal-iso = {ANTIBIOTICS-BASEL}, journal = {ANTIBIOTICS}, volume = {11}, unique-id = {32850862}, abstract = {Global crop production depends on strategies to counteract the ever‐increasing spread of plant pathogens. Antibiotics are often used for large‐scale treatments. As a result, Erwinia amylovora, causal agent of the contagious fire blight disease, has already evolved resistance to streptomycin (Sm). Photodynamic Inactivation (PDI) of microorganisms has been introduced as innovative method for plant protection. The aim of this study is to demonstrate that E. amylovora resistant to Sm (E. amylovoraSmR) can be killed by PDI. Two photosensitizers, the synthetic B17‐0024, and the natural derived anionic sodium magnesium chlorophyllin (Chl) with cell‐wall‐permeabilizing agents are compared in terms of their photo‐killing efficiency in liquid culture with or without 100 μg/mL Sm. In vitro experiments were performed at photosensitizer concentrations of 1, 10 or 100 μM and 5 or 30 min incubation in the dark, followed by illumination at 395 nm (radiant exposure 26.6 J/cm2). The highest inactivation of seven log steps was achieved at 100 μM B17‐0024 after 30 min incubation. Shorter incubation (5 min), likely to represent field conditions, reduced the photokilling to 5 log steps. Chlorophyllin at 100 μM in combination with 1.2% polyaspartic acid (PASA) reduced the number of bacteria by 6 log steps. While PASA itself caused some light independent toxicity, an antibacterial effect (3 log reduction) was achieved only in combination with Chl, even at concentrations as low as 10 μM. Addition of 100 μg/ml Sm to media did not significantly increase the efficacy of the photodynamic treatment. This study proves principle that PDI can be used to treat plant diseases even if causative bacteria are resistant to conventional treatment. Therefore, PDI based on natural photosensitizers might represent an eco‐friendly treatment strategy especially in organic farming. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.}, keywords = {ARTICLE; SODIUM; MAGNESIUM; nonhuman; TOXICITY; organic farming; unclassified drug; antibacterial activity; bacterium culture; bacterial growth; streptomycin; streptomycin; Antibiotic resistance; photodynamic therapy; photosensitizing agent; illumination; plant disease; plant disease; natural product; Fire blight; Fire blight; Erwinia amylovora; Erwinia amylovora; cell permeabilization; CHLOROPHYLL; ANTIMICROBIAL RESISTANCE; natural compounds; photodynamic inactivation; polyaspartic acid; chlorophyllin; B17 0024}, year = {2022}, eissn = {2079-6382} } @article{MTMT:32598570, title = {Dextran and peptide-based pH-sensitive hydrogel boosts healing process in multidrug-resistant bacteria-infected wounds}, url = {https://m2.mtmt.hu/api/publication/32598570}, author = {Wu, S. and Yang, Y. and Wang, S. and Dong, C. and Zhang, X. and Zhang, R. and Yang, L.}, doi = {10.1016/j.carbpol.2021.118994}, journal-iso = {CARBOHYD POLYM}, journal = {CARBOHYDRATE POLYMERS}, volume = {278}, unique-id = {32598570}, issn = {0144-8617}, abstract = {Traumatic multidrug-resistant (MDR) bacterial infections are deadly threat to the public. To combat MDR bacteria, we developed a dual functional pH-sensitive hydrogel based on peptide DP7 (VQWRIRVAVIRK) and oxidized dextran (DP7-ODEX hydrogel). As an antimicrobial peptide, DP7 can synergize with many antibiotics; thus, we loaded ceftazidime into DP7-ODEX hydrogel, which showed an obvious advantage in MDR P. aeruginosa inhibition. Additionally, due to the interaction between aldehyde groups in oxidized dextran and amine groups from wound tissue, the hydrogel could extend on the irregular surface of skin defects and promote epithelial cells adhesion. DP7 could also be used as a wound-healing peptide and accelerate the healing process. We confirmed that the DP7-ODEX hydrogel exerted formidable therapeutic effects in normal or diabetic wound infection model. According to histomorphology analysis we found that DP7 hydrogel also have a scarless wound healing ability. In summary, we developed a hydrogel fabricated by the dual functional peptide DP7 that can kill multidrug-resistant bacteria colonizing the wound bed and boost scarless wound healing. © 2021 Elsevier Ltd}, keywords = {PEPTIDES; BACTERIA; Wound healing; Wound healing; dextran; dextran; Hydrogels; ANTIBACTERIAL PEPTIDES; resistant bacteria; Multidrug resistants; ANTIBACTERIAL PEPTIDE; multidrug-resistant bacteria; pH Sensors; Healing process; MDR bacteria; PH-SENSITIVE HYDROGEL; DP7; DP7; Oxidized dextrans; Scarless wound healing}, year = {2022}, eissn = {1879-1344} }