@article{MTMT:3378998, title = {Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides}, url = {https://m2.mtmt.hu/api/publication/3378998}, author = {Lázár, Viktória and Martins, Ana and Spohn, Réka and Daruka, Lejla and Grézal, Gábor and Fekete, Gergely and Számel, Mónika and Jangir, Pramod Kumar and Kintses, Bálint and Csörgő, Bálint and Nyerges, Ákos and Györkei, Ádám and Kincses, András and Dér, András and Walter, Fruzsina and Deli, Mária Anna and Zsoldiné Urbán, Edit and Hegedüs, Zsófia and Olajos, Gábor and Méhi, Orsolya Katinka and Bálint, Balázs and Nagy, István and Martinek, Tamás and Papp, Balázs and Pál, Csaba}, doi = {10.1038/s41564-018-0164-0}, journal-iso = {NAT MICROBIOL}, journal = {NATURE MICROBIOLOGY}, volume = {3}, unique-id = {3378998}, issn = {2058-5276}, abstract = {Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections.}, year = {2018}, eissn = {2058-5276}, pages = {718-731}, orcid-numbers = {Grézal, Gábor/0000-0003-1685-4791; Jangir, Pramod Kumar/0000-0001-8330-0655; Csörgő, Bálint/0000-0003-0397-6845; Nyerges, Ákos/0000-0002-1581-490X; Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524; Zsoldiné Urbán, Edit/0000-0002-9602-7552; Hegedüs, Zsófia/0000-0002-5546-8167; Olajos, Gábor/0000-0002-2479-4891; Méhi, Orsolya Katinka/0009-0004-7918-913X; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:3365532, title = {Comparison of a rat primary cell-based blood-brain barrier model with epithelial and brain endothelial cell lines: gene expression and drug transport}, url = {https://m2.mtmt.hu/api/publication/3365532}, author = {Veszelka, Szilvia and Tóth, András and Walter, Fruzsina and Tóth, Andrea and Gróf, Ilona and Mészáros, Mária and Bocsik, Alexandra and Virághné Hellinger, Éva and Vastag, M and Rákhely, Gábor and Deli, Mária Anna}, doi = {10.3389/fnmol.2018.00166}, journal-iso = {FRONT MOL NEUROSCI}, journal = {FRONTIERS IN MOLECULAR NEUROSCIENCE}, volume = {11}, unique-id = {3365532}, issn = {1662-5099}, abstract = {Cell culture-based blood-brain barrier (BBB) models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC), ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA). As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L), and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1) and influx transporters (GLUT-1, LAT-1) were present in all models at mRNA levels. The transcript of BCRP (ABCG2) was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6,-9, MCT6,-8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which are substrates of these transporters. Brain endothelial cell lines GP8, RBE4, D3 and D3L did not form a restrictive paracellular barrier necessary for screening small molecular weight pharmacons. Therefore, among the tested culture models, the primary cell-based EPA model is suitable for the functional analysis of the BBB. © 2018 Veszelka, Tóth, Walter, Tóth, Gróf, Mészáros, Bocsik, Hellinger, Vastag, Rákhely and Deli.}, keywords = {immunohistochemistry; ARTICLE; human; high performance liquid chromatography; multidrug resistance protein 1; controlled study; nonhuman; animal tissue; animal model; animal experiment; animal cell; valproic acid; gabapentin; Mass spectrometry; Gene Expression; Gene Expression; Blood-Brain Barrier; quality control; human cell; drug metabolism; protein expression; messenger rna; drug transport; unindexed drug; probenecid; ATORVASTATIN; salicylic acid; Cytochrome P450; blood brain barrier; drug penetration; real time polymerase chain reaction; Electric resistance; ABC transporter; rosuvastatin; pravastatin; ASTROCYTE; claudin 7; claudin 5; claudin 4; claudin 3; claudin 1; coculture; baclofen; MDCK; glucose transporter 1; amino acid transporter; Caco-2; donepezil; brain cell culture; Caco-2 cell line; glucose transporter 5; MONOCARBOXYLATE TRANSPORTER 1; tacrine; claudin 11; claudin 2; HBEC cell line (brain); epithelial cell line; tight junction protein; brain pericyte; transendothelial electrical resistance; Brain endothelial cells; CNS drug permeability; HCMEC/D3; RBE4; claudin 16; glucose transporter 3; solute carrier protein; rat}, year = {2018}, eissn = {1662-5099}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Rákhely, Gábor/0000-0003-2557-3641; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:3242472, title = {Claudin peptidomimetics modulate tissue barriers for enhanced drug delivery}, url = {https://m2.mtmt.hu/api/publication/3242472}, author = {Dithmer, S and Staat, C and Müller, C and Ku, M-C and Pohlmann, A and Niendorf, T and Gehne, N and Fallier-Becker, P and Kittel, Ágnes and Walter, Fruzsina and Veszelka, Szilvia and Deli, Mária Anna and Blasig, R and Haseloff, RF and Blasig, IE and Winkler, L}, doi = {10.1111/nyas.13359}, journal-iso = {ANN NY ACAD SCI}, journal = {ANNALS OF THE NEW YORK ACADEMY OF SCIENCES}, volume = {1397}, unique-id = {3242472}, issn = {0077-8923}, year = {2017}, eissn = {1749-6632}, pages = {169-184}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:3009615, title = {Reversible opening of intercellular junctions of intestinal epithelial and brain endothelial cells with tight junction modulator peptides}, url = {https://m2.mtmt.hu/api/publication/3009615}, author = {Bocsik, Alexandra and Walter, Fruzsina and Gyebrovszki, A and Fülöp, Lívia and Blasig, IE and Dabrowski, S and Ötvös, Ferenc and Tóth, András and Rákhely, Gábor and Veszelka, Szilvia and Vastag, M and Révész, Piroska and Deli, Mária Anna}, doi = {10.1016/j.xphs.2015.11.018}, journal-iso = {J PHARM SCI}, journal = {JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {105}, unique-id = {3009615}, issn = {0022-3549}, year = {2016}, eissn = {1520-6017}, pages = {754-765}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Fülöp, Lívia/0000-0002-8010-0129; Rákhely, Gábor/0000-0003-2557-3641; Révész, Piroska/0000-0002-5336-6052; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:2932595, title = {para-sulphonato-calix[n]arenes as selective activators for the passage of molecules across the Caco-2 model intestinal membrane}, url = {https://m2.mtmt.hu/api/publication/2932595}, author = {Róka, Eszter and Vecsernyés, Miklós and Bácskay, Ildikó and Félix, C and Rhimi, M and Coleman, AW and Perret, F}, doi = {10.1039/c5cc01777g}, journal-iso = {CHEM COMMUN}, journal = {CHEMICAL COMMUNICATIONS}, volume = {51}, unique-id = {2932595}, issn = {1359-7345}, year = {2015}, eissn = {1364-548X}, pages = {9374-9376} } @article{MTMT:2709800, title = {Sucrose esters increase drug penetration, but do not inhibit P-glycoprotein in Caco-2 intestinal epithelial cells}, url = {https://m2.mtmt.hu/api/publication/2709800}, author = {Kiss, Lóránd and Virághné Hellinger, Éva and Pilbat, Ana Maria and Kittel, Ágnes and Török, Zsolt and Füredi, András and Szakács, Gergely and Veszelka, Szilvia and Sipos, Péter and Ózsvári, B and Puskás, László and Vastag, M and Révész, Piroska and Deli, Mária Anna}, doi = {10.1002/jps.24085}, journal-iso = {J PHARM SCI}, journal = {JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {103}, unique-id = {2709800}, issn = {0022-3549}, abstract = {Sucrose fatty acid esters are increasingly used as excipients in pharmaceutical products, but few data are available on their toxicity profile, mode of action, and efficacy on intestinal epithelial models. Three water-soluble sucrose esters, palmitate (P-1695), myristate (M-1695), laurate (D-1216), and two reference absorption enhancers, Tween 80 and Cremophor RH40, were tested on Caco-2 cells. Caco-2 monolayers formed a good barrier as reflected by high transepithelial resistance and positive immunostaining for junctional proteins claudin-1, ZO-1, and -catenin. Sucrose esters in nontoxic concentrations significantly reduced resistance and impedance, and increased permeability for atenolol, fluorescein, vinblastine, and rhodamine 123 in Caco-2 monolayers. No visible opening of the tight junctions was induced by sucrose esters assessed by immunohistochemistry and electron microscopy, but some alterations were seen in the structure of filamentous actin microfilaments. Sucrose esters fluidized the plasma membrane and enhanced the accumulation of efflux transporter ligands rhodamine 123 and calcein AM in epithelial cells, but did not inhibit the P-glycoprotein (P- gp)-mediated calcein AM accumulation in MES-SA/Dx5 cell line. These data indicate that in addition to their dissolution-increasing properties sucrose esters can enhance drug permeability through both the transcellular and paracellular routes without inhibiting P-}, year = {2014}, eissn = {1520-6017}, pages = {3107-3119}, orcid-numbers = {Füredi, András/0000-0002-7883-9901; Révész, Piroska/0000-0002-5336-6052; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:2034983, title = {Comparison of brain capillary endothelial cell based and epithelial cell based (MDCK-MDR1, Caco-2, and VB-Caco-2) surrogate blood-brain barrier penetration models}, url = {https://m2.mtmt.hu/api/publication/2034983}, author = {Virághné Hellinger, Éva and Veszelka, Szilvia and Tóth, Andrea and Walter, Fruzsina and Kittel, Ágnes and Bakk, ML and Tihanyi, Károly and Háda, Viktor and Nakagawa, S and Thuy, DH and Niwa, M and Deli, Mária Anna and Vastag, M}, doi = {10.1016/j.ejpb.2012.07.020}, journal-iso = {EUR J PHARM BIOPHARM}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS}, volume = {82}, unique-id = {2034983}, issn = {0939-6411}, year = {2012}, eissn = {1873-3441}, pages = {340-351}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:1847178, title = {The effect of sucrose esters on a culture model of the nasal barrier}, url = {https://m2.mtmt.hu/api/publication/1847178}, author = {Kürti, Levente and Veszelka, Szilvia and Bocsik, Alexandra and Dung, Ngo Thi Khue and Ozsvari, B and Puskás, László and Kittel, Ágnes and Révész, Piroska and Deli, Mária Anna}, doi = {10.1016/j.tiv.2012.01.015}, journal-iso = {TOXICOL IN VITRO}, journal = {TOXICOLOGY IN VITRO}, volume = {26}, unique-id = {1847178}, issn = {0887-2333}, abstract = {Sucrose esters are effective solubilizers and there is an interest to use them as pharmaceutical excipients for nasal dru1 delivery. We have determined for the first time the non-toxic doses of laurate and myristate sucrose esters by four independent methods, and their effects on epithelial permeability using RPMI 2650 human nasal epithelial cell line. Based on real-time cell electronic sensing, MTT dye conversion and lactate dehydrogenase release methods reference surfactant Cremophor RH40 proved to be the least toxic excipient, and could be used at 5mg/mL concentration for 1h in epithelial cells without cellular damage. The non-toxic dose of Tween 80 was 1mg/mL, while the dose of laurate and myristate sucrose esters that could be safely used on cells for 1h was 0.1mg/mL. Both the reference surfactants and the sucrose esters significantly enhanced the permeability of epithelial cell layers for the paracellular marker FITC-labelled 4.4kDa dextran at 0.1mg/mL concentration. The effects of sucrose esters on epithelial permeability were dose-dependent. These data indicate that laurate and myristate sucrose esters can be potentially used as permeability enhancers in nasal formulations to augment drug delivery to the systemic circulation.}, year = {2012}, eissn = {1879-3177}, pages = {445-454}, orcid-numbers = {Révész, Piroska/0000-0002-5336-6052; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:1753490, title = {Drug penetration model of vinblastine-treated Caco-2 cultures}, url = {https://m2.mtmt.hu/api/publication/1753490}, author = {Virághné Hellinger, Éva and Bakk, ML and Pócza, Péter and Tihanyi, Károly and Vastag, M}, doi = {10.1016/j.ejps.2010.05.015}, journal-iso = {EUR J PHARM SCI}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {41}, unique-id = {1753490}, issn = {0928-0987}, year = {2010}, eissn = {1879-0720}, pages = {96-106} } @article{MTMT:1920731, title = {Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery}, url = {https://m2.mtmt.hu/api/publication/1920731}, author = {Deli, Mária Anna}, doi = {10.1016/j.bbamem.2008.09.016}, journal-iso = {BBA-BIOMEMBRANES}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES}, volume = {1788}, unique-id = {1920731}, issn = {0005-2736}, year = {2009}, eissn = {1879-2642}, pages = {892-910}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524} }