@article{MTMT:34409072,
	title = {Acquired Triazole Resistance Alters Pathogenicity-Associated Features in Candida auris in an Isolate-Dependent Manner},
	url = {https://m2.mtmt.hu/api/publication/34409072},
	author = {Bohner, Flóra and Papp, Csaba Gergő and Takács, Tamás and Varga, Mónika and Szekeres, András and Nosanchuk, Joshua D. and Vágvölgyi, Csaba and Tóth, Renáta and Gácser, Attila},
	doi = {10.3390/jof9121148},
	journal-iso = {J FUNGI},
	journal = {JOURNAL OF FUNGI},
	volume = {9},
	unique-id = {34409072},
	abstract = {Fluconazole resistance is commonly encountered in Candida auris, and the yeast frequently displays resistance to other standard drugs, which severely limits the number of effective therapeutic agents against this emerging pathogen. In this study, we aimed to investigate the effect of acquired azole resistance on the viability, stress response, and virulence of this species. Fluconazole-, posaconazole-, and voriconazole- resistant strains were generated from two susceptible C. auris clinical isolates (0381, 0387) and compared under various conditions. Several evolved strains became pan-azole-resistant, as well as echinocandin-cross-resistant. While being pan-azole-resistant, the 0381-derived posaconazole-evolved strain colonized brain tissue more efficiently than any other strain, suggesting that fitness cost is not necessarily a consequence of resistance development in C. auris. All 0387-derived evolved strains carried a loss of function mutation (R160S) in BCY1, an inhibitor of the PKA pathway. Sequencing data also revealed that posaconazole treatment can result in ERG3 mutation in C. auris. Despite using the same mechanisms to generate the evolved strains, both genotype and phenotype analysis highlighted that the development of resistance was unique for each strain. Our data suggest that C. auris triazole resistance development is a highly complex process, initiated by several pleiotropic factors.},
	year = {2023},
	eissn = {2309-608X},
	orcid-numbers = {Papp, Csaba Gergő/0000-0003-4450-0667; Szekeres, András/0000-0003-1651-4623; Nosanchuk, Joshua D./0000-0001-9905-5754; Vágvölgyi, Csaba/0000-0003-0009-7773; Tóth, Renáta/0000-0001-7395-0689}
}

@article{MTMT:34043893,
	title = {Hard nut to crack: Solving the disulfide linkage pattern of the Neosartorya (Aspergillus) fischeri antifungal protein 2},
	url = {https://m2.mtmt.hu/api/publication/34043893},
	author = {Váradi, Györgyi and Kele, Zoltán and Czajlik, András and Borics, Attila and Bende, Gábor and Papp, Csaba Gergő and Rákhely, Gábor and Tóth, Gábor and Batta, Gyula and Galgóczi, László Norbert},
	doi = {10.1002/pro.4692},
	journal-iso = {PROTEIN SCI},
	journal = {PROTEIN SCIENCE},
	volume = {32},
	unique-id = {34043893},
	issn = {0961-8368},
	abstract = {As a consequence of the fast resistance spreading, a limited number of drugs are available to treat fungal infections. Therefore, there is an urgent need to develop new antifungal treatment strategies. The features of a disulfide bond-stabilized antifungal protein, NFAP2 secreted by the mold Neosartorya (Aspergillus) fischeri render it to be a promising template for future protein-based antifungal drug design, which requires knowledge about the native disulfide linkage pattern as it is one of the prerequisites for biological activity. However, in the lack of tryptic and chymotryptic proteolytic sites in the ACNCPNNCK sequence, the determination of the disulfide linkage pattern of NFAP2 is not easy with traditional mass spectrometry-based methods. According to in silico predictions working with a preliminary nuclear magnetic resonance (NMR) solution structure, two disulfide isomers of NFAP2 (abbacc and abbcac) were possible. Both were chemically synthesized; and comparative reversed-phase high-performance liquid chromatography, electronic circular dichroism and NMR spectroscopy analyses, and antifungal susceptibility and efficacy tests indicated that the abbcac is the native pattern. This knowledge allowed rational modification of NAFP2 to improve the antifungal efficacy and spectrum through the modulation of the evolutionarily conserved gamma-core region, which is responsible for the activity of several antimicrobial peptides. Disruption of the steric structure of NFAP2 upon gamma-core modification led to the conclusions that this motif may affect the formation of the biologically active three-dimensional structure, and that the gamma-core modulation is not an efficient tool to improve the antifungal efficacy or to change the antifungal spectrum of NFAP2.},
	keywords = {DYNAMICS; PREDICTION; DRUG DESIGN; BONDS; protein structure; ANTIFUNGAL PROTEIN; disulfide linkage pattern},
	year = {2023},
	eissn = {1469-896X},
	orcid-numbers = {Váradi, Györgyi/0000-0001-7907-8908; Kele, Zoltán/0000-0002-4401-0302; Papp, Csaba Gergő/0000-0003-4450-0667; Rákhely, Gábor/0000-0003-2557-3641; Tóth, Gábor/0000-0002-3604-4385; Batta, Gyula/0000-0002-0442-1828; Galgóczi, László Norbert/0000-0002-6976-8910}
}

@CONFERENCE{MTMT:33576180,
	title = {ACQUISITION OF ANTIFUNGAL RESISTANCE INFLUENCES VIRULENCE ATTRIBUTES OF CANDIDA AURIS MICROEVOLVED STRAINS IN MOUSE SYSTEMIC FUNGAL INFECTION MODEL},
	url = {https://m2.mtmt.hu/api/publication/33576180},
	author = {Bohner, Flóra and Papp, Csaba Gergő and Takács, Tamás and Szekeres, András and Varga, Mónika and Vágvölgyi, Csaba and Tóth, Renáta and Gácser, Attila},
	booktitle = {A Magyar Mikrobiológiai Társaság 2022. évi Nagygyűlése és a XV. Fermentációs Kollokvium},
	unique-id = {33576180},
	year = {2022},
	pages = {11},
	orcid-numbers = {Papp, Csaba Gergő/0000-0003-4450-0667; Szekeres, András/0000-0003-1651-4623; Vágvölgyi, Csaba/0000-0003-0009-7773; Tóth, Renáta/0000-0001-7395-0689}
}

@{MTMT:33255670,
	title = {Antifungal effect of a novel defensin from Solanum lycopersicum L., and it's γ-core peptide derivatives},
	url = {https://m2.mtmt.hu/api/publication/33255670},
	author = {Tóth, Liliána and Papp, Rebeka and Váradi, Györgyi and Tóth, K Gábor and Papp, Csaba Gergő and Rákhely, Gábor and Poór, Péter and Galgóczi, László Norbert},
	booktitle = {„FIBOK 2022” : Fiatal Biotechnológusok V. Országos Konferenciája},
	unique-id = {33255670},
	year = {2022},
	pages = {33-33},
	orcid-numbers = {Tóth, Liliána/0000-0003-1400-6174; Papp, Csaba Gergő/0000-0003-4450-0667; Poór, Péter/0000-0002-4539-6358; Galgóczi, László Norbert/0000-0002-6976-8910}
}

@CONFERENCE{MTMT:33252438,
	title = {Characterization of NFAP2 resistance-evolved Candida albicans strains},
	url = {https://m2.mtmt.hu/api/publication/33252438},
	author = {Bende, Gábor and Zsindely, Nóra and Bodai, László and Krisztián, Laczi and Papp, Csaba Gergő and Attila, Farkas and Zsolt, Kristóffy and Petra, Királdi and Gábor, Rákhely and Galgóczi, László Norbert},
	booktitle = {A Magyar Mikrobiológiai Társaság 2022. évi Nagygyűlése és a XV. Fermentációs Kollokvium},
	unique-id = {33252438},
	year = {2022},
	pages = {8-8},
	orcid-numbers = {Zsindely, Nóra/0000-0002-6189-3100; Bodai, László/0000-0001-8411-626X; Papp, Csaba Gergő/0000-0003-4450-0667; Galgóczi, László Norbert/0000-0002-6976-8910}
}

@{MTMT:33250266,
	title = {Antifungal activity of peptides designed on the γ–core of tomato plant defensins},
	url = {https://m2.mtmt.hu/api/publication/33250266},
	author = {Tóth, Liliána and Papp, Rebeka and Papp, Csaba Gergő and Váradi, Györgyi and Tóth, Gábor and Gábor, Rákhely and Poór, Péter and Galgóczi, László Norbert},
	booktitle = {FEMS Conference on Microbiology in association with Serbian Society of Microbiology},
	unique-id = {33250266},
	year = {2022},
	pages = {837-838},
	orcid-numbers = {Tóth, Liliána/0000-0003-1400-6174; Papp, Csaba Gergő/0000-0003-4450-0667; Poór, Péter/0000-0002-4539-6358; Galgóczi, László Norbert/0000-0002-6976-8910}
}

@article{MTMT:33069296,
	title = {The Membrane Activity of the Amphibian Temporin B Peptide Analog TB_KKG6K Sheds Light on the Mechanism That Kills Candida albicans},
	url = {https://m2.mtmt.hu/api/publication/33069296},
	author = {Kakar, Anant and Sastre-Velasquez, Luis Enrique and Hess, Michael and Galgóczi, László Norbert and Papp, Csaba Gergő and Holzknecht, Jeanett and Romanelli, Alessandra and Váradi, Györgyi and Malanovic, Nermina and Marx, Florentine},
	doi = {10.1128/msphere.00290-22},
	journal-iso = {MSPHERE},
	journal = {mSPHERE},
	volume = {7},
	unique-id = {33069296},
	issn = {2379-5042},
	abstract = {Fungal infections with the opportunistic human pathogen C. albicans are associated with high mortality rates in immunocompromised patients. This is partly due to the yeast's ability to rapidly develop resistance toward currently available antifungals. Temporin B (TB) is a 13-amino-acid-long, cationic peptide secreted by the granular glands of the European frog Rana temporaria. We recently showed that the modified TB peptide analog TB_KKG6K rapidly killed planktonic and sessile Candida albicans at low micromolar concentrations and was neither hemolytic nor cytotoxic to mammalian cells in vitro. The present study aimed to shed light into its mechanism of action, with a focus on its fungal cell membrane activity. We utilized different fluorescent dyes to prove that it rapidly induces membrane depolarization and permeabilization. Studies on model membrane systems revealed that the TB analog undergoes hydrophobic and electrostatic membrane interactions, showing a preference for anionic lipids, and identified phosphatidylinositol and cardiolipin as possible peptide targets. Fluorescence microscopy using fluorescein isothiocyanate-labeled TB_KKG6K in the presence of the lipophilic dye FM4-64 indicated that the peptide compromises membrane integrity and rapidly enters C. albicans cells in an energy-independent manner. Peptide-treated cells analyzed by cryo-based electron microscopy exhibited no signs of cell lysis; however, subcellular structures had disintegrated, suggesting that intracellular activity may form part of the killing mechanism of the peptide. Taken together, this study proved that TB_KKG6K compromises C. albicans membrane function, which explains the previously observed rapid, fungicidal mode of action and supports its great potential as a future anti-Candida therapeutic. IMPORTANCE Fungal infections with the opportunistic human pathogen C. albicans are associated with high mortality rates in immunocompromised patients. This is partly due to the yeast's ability to rapidly develop resistance toward currently available antifungals. Small, cationic, membrane-active peptides are promising compounds to fight against resistance development, as many of them effectuate rapid fungal cell death. This fast killing is believed to hamper the development of resistance, as the fungi do not have sufficient time to adapt to the antifungal compound. We previously reported that the synthetic variant of the amphibian TB peptide, TB_KKG6K, rapidly kills C. albicans. In the current study, the mechanism of action of the TB analog was investigated. We show that this TB analog is membrane-active and impairs cell membrane function, highlighting its potential to be developed as an attractive alternative anti-C. albicans therapeutic that may hinder the development of resistance.},
	keywords = {MODEL; DEPOLARIZATION; SECONDARY STRUCTURE; ANTIBACTERIAL; cholesterol; phosphatidylcholine; ANTIMICROBIAL PEPTIDES; Leakage; Candida albicans; permeabilization; LL-37; Cell-penetrating peptides; antifungal peptide; membrane activity; Temporin B; TB analog; GRAM-POSITIVE BACTERIAL},
	year = {2022},
	eissn = {2379-5042},
	orcid-numbers = {Galgóczi, László Norbert/0000-0002-6976-8910; Papp, Csaba Gergő/0000-0003-4450-0667}
}

@article{MTMT:33003489,
	title = {Functionalized Mesoporous Silica Nanoparticles for Drug-Delivery to Multidrug-Resistant Cancer Cells},
	url = {https://m2.mtmt.hu/api/publication/33003489},
	author = {Igaz, Nóra and Bélteky, Péter and Kovács, Dávid and Papp, Csaba Gergő and Rónavári, Andrea and Szabó, Diána and Gácser, Attila and Kónya, Zoltán and Csontné Kiricsi, Mónika},
	doi = {10.2147/IJN.S363952},
	journal-iso = {INT J NANOMED},
	journal = {INTERNATIONAL JOURNAL OF NANOMEDICINE},
	volume = {17},
	unique-id = {33003489},
	issn = {1176-9114},
	abstract = {Background: Multidrug resistance is a common reason behind the failure of chemotherapy. Even if the therapy is effective, serious adverse effects might develop due to the low specificity and selectivity of antineoplastic agents. Mesoporous silica nanoparticles (MSNs) are promising materials for tumor-targeting and drug-delivery due to their small size, relatively inert nature, and extremely large specific surfaces that can be functionalized by therapeutic and targeting entities. We aimed to create a fluorescently labeled MSN-based drug-delivery system and investigate their internalization and drug-releasing capability in drug-sensitive MCF-7 and P-glycoprotein-overexpressing multidrug-resistant MCF-7 KCR cancer cells.Methods and Results: To track the uptake and subcellular distribution of MSNs, particles with covalently coupled red fluorescent Rhodamine B (RhoB) were produced (RhoB@MSNs). Both MCF-7 and MCF-7 KCR cells accumulated a significant amount of RhoB@MSNs. The intracellular RhoB@MSN concentrations did not differ between sensitive and multidrug-resistant cells and were kept at the same level even after cessation of RhoB@MSN exposure. Although most RhoB@MSNs resided in the cytoplasm, significantly more RhoB@MSNs co-localized with lysosomes in multidrug-resistant cells compared to sensitive counterparts. To examine the drug-delivery capability of these particles, RhoB@Rho123@MSNs were established, where RhoB-functionalized nanoparticles carried green fluorescent Rhodamine 123 (Rho123) -a P-glycoprotein substrate - as cargo within mesopores. Significantly higher Rho123 fluorescence intensity was detected in RhoB@Rho123@MSN-treated multidrug-resistant cells than in free Rho123-exposed counterparts. The exceptional drug-delivery potential of MSNs was further verified using Mitomycin C (MMC)-loaded RhoB@MSNs (RhoB@MMC@MSNs). Exposures to RhoB@MMC@MSNs significantly decreased the viability not only of drug-sensitive but of multidrug-resistant cells and the elimination of MDR cells was significantly more robust than upon free MMC treatments.Conclusion: The efficient delivery of Rho123 and MMC to multidrug-resistant cells via MSNs, the amplified and presumably prolonged intracellular drug concentration, and the consequently enhanced cytotoxic effects envision the enormous potential of MSNs to defeat multidrug-resistant cancer.},
	year = {2022},
	eissn = {1178-2013},
	pages = {3079-3096},
	orcid-numbers = {Igaz, Nóra/0000-0003-1580-4397; Papp, Csaba Gergő/0000-0003-4450-0667; Rónavári, Andrea/0000-0001-7054-0975; Kónya, Zoltán/0000-0002-9406-8596; Csontné Kiricsi, Mónika/0000-0002-8416-2052}
}

@article{MTMT:32763732,
	title = {The effect of antifungal resistance development on the virulence of Candida species},
	url = {https://m2.mtmt.hu/api/publication/32763732},
	author = {Bohner, Flóra and Papp, Csaba Gergő and Gácser, Attila},
	doi = {10.1093/femsyr/foac019},
	journal-iso = {FEMS YEAST RES},
	journal = {FEMS YEAST RESEARCH},
	volume = {22},
	unique-id = {32763732},
	issn = {1567-1356},
	year = {2022},
	eissn = {1567-1364},
	orcid-numbers = {Papp, Csaba Gergő/0000-0003-4450-0667}
}

@article{MTMT:32655436,
	title = {The combination of Neosartorya (Aspergillus) fischeri antifungal proteins with rationally designed γ-core peptide derivatives is effective for plant and crop protection},
	url = {https://m2.mtmt.hu/api/publication/32655436},
	author = {Tóth, Liliána and Poór, Péter and Ördög, Attila and Váradi, Györgyi and Farkas, Attila and Papp, Csaba Gergő and Bende, Gábor and Tóth, Gábor and Rákhely, Gábor and Marx, Florentine and Galgóczi, László Norbert},
	doi = {10.1007/s10526-022-10132-y},
	journal-iso = {BIOCONTROL},
	journal = {BIOCONTROL},
	volume = {67},
	unique-id = {32655436},
	issn = {1386-6141},
	abstract = {Plant pathogenic fungi are responsible for enormous crop losses worldwide. Overcoming this problem is challenging as these fungi can be highly resistant to approved chemical fungicides. There is thus a need to develop and introduce fundamentally new plant and crop protection strategies for sustainable agricultural production. Highly stable extracellular antifungal proteins (AFPs) and their rationally designed peptide derivatives (PDs) constitute feasible options to meet this challenge. In the present study, their potential for topical application to protect plants and crops as combinatorial biofungicides is supported by the investigation of two Neosartorya (Aspergillus) fischeri AFPs (NFAP and NFAP2) and their γ-core PDs. Previously, the biofungicidal potential of NFAP, its rationally designed γ-core PD (γNFAP-opt), and NFAP2 was reported. Susceptibility tests in the present study extended the in vitro antifungal spectrum of NFAP2 and its γ-core PD (γNFAP2-opt) to Botrytis, Cladosporium, and Fusarium spp. Besides, in vitro additive or indifferent interactions, and synergism were observed when NFAP or NFAP2 was applied in combination with γNFAP-opt. Except for γNFAP2-opt, the investigated proteins and peptides did not show any toxicity to tomato plant leaves. The application of NFAP in combination with γNFAP-opt effectively inhibited conidial germination, biofilm formation, and hyphal extension of the necrotrophic mold Botrytis cinerea on tomato plant leaves. However, the same combination only partially impeded the B. cinerea-mediated decay of tomato fruits, but mitigated the symptoms. Our results highlight the feasibility of using the combination of AFP and PD as biofungicide for the fungal infection control in plants and crops.},
	keywords = {drug combination; Synergism; Plant pathogenic fungus; Biofungicide; Neosartorya (Aspergillus) fischeri antifungal proteins; γ-core peptide},
	year = {2022},
	eissn = {1573-8248},
	pages = {249-262},
	orcid-numbers = {Tóth, Liliána/0000-0003-1400-6174; Poór, Péter/0000-0002-4539-6358; Ördög, Attila/0000-0002-1867-8237; Váradi, Györgyi/0000-0001-7907-8908; Papp, Csaba Gergő/0000-0003-4450-0667; Tóth, Gábor/0000-0002-3604-4385; Rákhely, Gábor/0000-0003-2557-3641; Galgóczi, László Norbert/0000-0002-6976-8910}
}