@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} } @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:32106320, title = {Limited evolutionary conservation of multidrug resistance and collateral sensitivity (vol 36, pg 1601, 2019)}, url = {https://m2.mtmt.hu/api/publication/32106320}, author = {Apjok, Gábor and Boross, Gábor and Nyerges, Ákos and Fekete, Gergely and Lázár, Viktória and Papp, Balázs and Pál, Csaba and Csörgő, Bálint}, doi = {10.1093/molbev/msab116}, journal-iso = {MOL BIOL EVOL}, journal = {MOLECULAR BIOLOGY AND EVOLUTION}, volume = {38}, unique-id = {32106320}, issn = {0737-4038}, keywords = {evolutionary biology; Biochemistry & Molecular Biology}, year = {2021}, eissn = {1537-1719}, pages = {3029-3029}, orcid-numbers = {Boross, Gábor/0000-0002-7208-5678; Nyerges, Ákos/0000-0002-1581-490X; Csörgő, Bálint/0000-0003-0397-6845} } @article{MTMT:32655233, title = {Transient antibiotic resistance calls for attention}, url = {https://m2.mtmt.hu/api/publication/32655233}, author = {Lázár, Viktória and Kishony, Roy}, doi = {10.1038/s41564-019-0571-x}, journal-iso = {NAT MICROBIOL}, journal = {NATURE MICROBIOLOGY}, volume = {4}, unique-id = {32655233}, issn = {2058-5276}, year = {2019}, eissn = {2058-5276}, pages = {1606-1607}, orcid-numbers = {Kishony, Roy/0000-0002-5013-5072} } @article{MTMT:31038930, title = {Chemical-genetic profiling reveals limited cross-resistance between antimicrobial peptides with different modes of action}, url = {https://m2.mtmt.hu/api/publication/31038930}, author = {Kintses, Bálint and Jangir, Pramod Kumar and Fekete, Gergely and Számel, Mónika and Méhi, Orsolya Katinka and Spohn, Réka and Daruka, Lejla and Martins, Ana and Hosseinnia, A. and Gagarinova, A. and Kim, S. and Phanse, S. and Csörgő, Bálint and Györkei, Ádám and Ari, Eszter and Lázár, Viktória and Nagy, István and Babu, M. and Pál, Csaba and Papp, Balázs}, doi = {10.1038/s41467-019-13618-z}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {10}, unique-id = {31038930}, issn = {2041-1723}, year = {2019}, eissn = {2041-1723}, orcid-numbers = {Jangir, Pramod Kumar/0000-0001-8330-0655; Méhi, Orsolya Katinka/0009-0004-7918-913X; Csörgő, Bálint/0000-0003-0397-6845; Ari, Eszter/0000-0001-7774-1067} } @article{MTMT:30865039, title = {Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance}, url = {https://m2.mtmt.hu/api/publication/30865039}, author = {Spohn, Réka and Daruka, Lejla and Lázár, Viktória and Martins, Ana and Vidovics, Fanni and Grézal, Gábor and Méhi, Orsolya Katinka and Kintses, Bálint and Számel, Mónika and Jangir, Pramod Kumar and Csörgő, Bálint and Györkei, Ádám and Bódi, Zoltán and Faragó, Anikó and Bodai, László and Földesi, Imre and Kata, Diána and Maróti, Gergely and Pap, Bernadett and Wirth, Roland and Papp, Balázs and Pál, Csaba}, doi = {10.1038/s41467-019-12364-6}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {10}, unique-id = {30865039}, issn = {2041-1723}, abstract = {Antimicrobial peptides (AMPs) are promising antimicrobials, however, the potential of bacterial resistance is a major concern. Here we systematically study the evolution of resistance to 14 chemically diverse AMPs and 12 antibiotics in Escherichia coli. Our work indicates that evolution of resistance against certain AMPs, such as tachyplesin II and cecropin P1, is limited. Resistance level provided by point mutations and gene amplification is very low and antibiotic-resistant bacteria display no cross-resistance to these AMPs. Moreover, genomic fragments derived from a wide range of soil bacteria confer no detectable resistance against these AMPs when introduced into native host bacteria on plasmids. We have found that simple physicochemical features dictate bacterial propensity to evolve resistance against AMPs. Our work could serve as a promising source for the development of new AMP-based therapeutics less prone to resistance, a feature necessary to avoid any possible interference with our innate immune system.}, year = {2019}, eissn = {2041-1723}, orcid-numbers = {Grézal, Gábor/0000-0003-1685-4791; Méhi, Orsolya Katinka/0009-0004-7918-913X; Jangir, Pramod Kumar/0000-0001-8330-0655; Csörgő, Bálint/0000-0003-0397-6845; Bodai, László/0000-0001-8411-626X; Földesi, Imre/0000-0002-3329-8136; Kata, Diána/0000-0002-4432-9380; Maróti, Gergely/0000-0002-3705-0461; Wirth, Roland/0000-0002-2383-2323} } @article{MTMT:30776198, title = {Rapid decline of bacterial drug-resistance in an antibiotic-free environment through phenotypic reversion.}, url = {https://m2.mtmt.hu/api/publication/30776198}, author = {Dunai, Anett and Spohn, Réka and Farkas, Zoltán and Lázár, Viktória and Györkei, Ádám and Apjok, Gábor and Boross, Gábor and Szappanos, Balázs and Grézal, Gábor and Faragó, Anikó and Bodai, László and Papp, Balázs and Pál, Csaba}, doi = {10.7554/eLife.47088}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {8}, unique-id = {30776198}, issn = {2050-084X}, abstract = {Antibiotic resistance typically induces a fitness cost that shapes the fate of antibiotic-resistant bacterial populations. However, the cost of resistance can be mitigated by compensatory mutations elsewhere in the genome, and therefore the loss of resistance may proceed too slowly to be of practical importance. We present our study on the efficacy and phenotypic impact of compensatory evolution in Escherichia coli strains carrying multiple resistance mutations. We have demonstrated that drug-resistance frequently declines within 480 generations during exposure to an antibiotic-free environment. The extent of resistance loss was found to be generally antibiotic-specific, driven by mutations that reduce both resistance level and fitness costs of antibiotic-resistance mutations. We conclude that phenotypic reversion to the antibiotic-sensitive state can be mediated by the acquisition of additional mutations, while maintaining the original resistance mutations. Our study indicates that restricting antimicrobial usage could be a useful policy, but for certain antibiotics only.}, keywords = {EVOLUTION; Antibiotic resistance; E. coli; evolutionary biology; compensatory mutations}, year = {2019}, eissn = {2050-084X}, orcid-numbers = {Boross, Gábor/0000-0002-7208-5678; Szappanos, Balázs/0000-0002-5075-1799; Grézal, Gábor/0000-0003-1685-4791; Bodai, László/0000-0001-8411-626X} } @article{MTMT:30703953, title = {Limited evolutionary conservation of the phenotypic effects of antibiotic resistance mutations}, url = {https://m2.mtmt.hu/api/publication/30703953}, author = {Apjok, Gábor and Boross, Gábor and Nyerges, Ákos and Fekete, Gergely and Lázár, Viktória and Papp, Balázs and Pál, Csaba and Csörgő, Bálint}, doi = {10.1093/molbev/msz109}, journal-iso = {MOL BIOL EVOL}, journal = {MOLECULAR BIOLOGY AND EVOLUTION}, volume = {36}, unique-id = {30703953}, issn = {0737-4038}, year = {2019}, eissn = {1537-1719}, pages = {1601-1611}, orcid-numbers = {Boross, Gábor/0000-0002-7208-5678; Nyerges, Ákos/0000-0002-1581-490X; Csörgő, Bálint/0000-0003-0397-6845} } @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:32029283, title = {Erratum: Correction: Phenotypic heterogeneity promotes adaptive evolution (PLoS biology (2017) 15 5 (e2000644))}, url = {https://m2.mtmt.hu/api/publication/32029283}, author = {Bódi, Zoltán and Farkas, Zoltán and Nevozhay, D. and Kalapis, Dorottya and Lázár, Viktória and Csörgő, Bálint and Nyerges, Ákos and Szamecz, Béla and Fekete, Gergely and Papp, Balázs and Araújo, H. and Oliveira, J.L. and Moura, G. and Santos, M.A.S. and Székely, T. Jr and Balázsi, G. and Pál, Csaba}, doi = {10.1371/journal.pbio.1002607}, journal-iso = {PLOS BIOL}, journal = {PLOS BIOLOGY}, volume = {15}, unique-id = {32029283}, issn = {1544-9173}, abstract = {[This corrects the article DOI: 10.1371/journal.pbio.2000644.].}, keywords = {ERROR; erratum}, year = {2017}, eissn = {1545-7885}, pages = {e1002607}, orcid-numbers = {Csörgő, Bálint/0000-0003-0397-6845; Nyerges, Ákos/0000-0002-1581-490X} }