@article{MTMT:34067381, title = {Phase-separated ribosome-nascent chain complexes in genotoxic stress response}, url = {https://m2.mtmt.hu/api/publication/34067381}, author = {Szatmári, Orsolya and Nagy-Mikó, Bence and Györkei, Ádám and Varga, Dániel and H. Kovács, Bálint Barna and Igaz, Nóra and Bognár, Bence and Rázga, Zsolt and Nagy, Gábor and Zsindely, Nóra and Bodai, László and Papp, Balázs and Erdélyi, Miklós and Csontné Kiricsi, Mónika and Blastyák, András and Collart, Martine A and Boros, Imre Miklós and Villanyi, Zoltan}, doi = {10.1261/rna.079755.123}, journal-iso = {RNA}, journal = {RNA-A PUBLICATION OF THE RNA SOCIETY}, volume = {29}, unique-id = {34067381}, issn = {1355-8382}, abstract = {Assemblysomes are EDTA- and RNase-resistant ribonucleoprotein (RNP) complexes of paused ribosomes with protruding nascent polypeptide chains. They have been described in yeast and human cells for the proteasome subunit Rpt1, and the disordered N-terminal part of the nascent chain was found to be indispensable for the accumulation of the Rpt1-RNP into assemblysomes. Motivated by this, to find other assemblysome-associated RNPs we used bioinformatics to rank subunits of Saccharomyces cerevisiae protein complexes according to their N-terminal disorder propensity. The results revealed that gene products involved in DNA repair are enriched among the top candidates. The Sgs1 DNA helicase was chosen for experimental validation. We found that indeed nascent chains of Sgs1 form EDTA-resistant RNP condensates, assemblysomes by definition. Moreover, upon exposure to UV, SGS1 mRNA shifted from assemblysomes to polysomes, suggesting that external stimuli are regulators of assemblysome dynamics. We extended our studies to human cell lines. The BLM helicase, ortholog of yeast Sgs1, was identified upon sequencing assemblysome-associated RNAs from the MCF7 human breast cancer cell line, and mRNAs encoding DNA repair proteins were overall enriched. Using the radiation-resistant A549 cell line, we observed by transmission electron microscopy that 1,6-hexanediol, an agent known to disrupt phase-separated condensates, depletes ring ribosome structures compatible with assemblysomes from the cytoplasm of cells and makes the cells more sensitive to X-ray treatment. Taken together these findings suggest that assemblysomes may be a component of the DNA damage response from yeast to human.}, year = {2023}, eissn = {1469-9001}, pages = {1557-1574}, orcid-numbers = {Varga, Dániel/0000-0003-0391-5057; Igaz, Nóra/0000-0003-1580-4397; Rázga, Zsolt/0000-0003-4717-8482; Nagy, Gábor/0000-0001-5464-1135; Zsindely, Nóra/0000-0002-6189-3100; Bodai, László/0000-0001-8411-626X; Erdélyi, Miklós/0000-0002-9501-5752; Csontné Kiricsi, Mónika/0000-0002-8416-2052; Boros, Imre Miklós/0000-0001-8504-9687} } @mastersthesis{MTMT:34109172, title = {Az in vivo fehérjeaggregáció útvonalait befolyásoló tényezők vizsgálata Escherichia coliban [Investigation of factors influencing routes of in vivo protein aggregation in Escherichia coli]}, url = {https://m2.mtmt.hu/api/publication/34109172}, author = {Györkei, Ádám}, doi = {10.14232/phd.11273}, publisher = {Universití of Szeged}, unique-id = {34109172}, year = {2022} } @article{MTMT:32813213, title = {Proteome-wide landscape of solubility limits in a bacterial cell}, url = {https://m2.mtmt.hu/api/publication/32813213}, author = {Györkei, Ádám and Daruka, Lejla and Balogh, Dávid and Őszi, Erika and Magyar, Zoltán and Szappanos, Balázs and Fekete, Gergely and Fuxreiter, Mónika and Horváth, Péter and Pál, Csaba and Kintses, Bálint and Papp, Balázs}, doi = {10.1038/s41598-022-10427-1}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {12}, unique-id = {32813213}, issn = {2045-2322}, abstract = {Proteins are prone to aggregate when expressed above their solubility limits. Aggregation may occur rapidly, potentially as early as proteins emerge from the ribosome, or slowly, following synthesis. However, in vivo data on aggregation rates are scarce. Here, we classified the Escherichia coli proteome into rapidly and slowly aggregating proteins using an in vivo image-based screen coupled with machine learning. We find that the majority (70%) of cytosolic proteins that become insoluble upon overexpression have relatively low rates of aggregation and are unlikely to aggregate co-translationally. Remarkably, such proteins exhibit higher folding rates compared to rapidly aggregating proteins, potentially implying that they aggregate after reaching their folded states. Furthermore, we find that a substantial fraction (similar to 35%) of the proteome remain soluble at concentrations much higher than those found naturally, indicating a large margin of safety to tolerate gene expression changes. We show that high disorder content and low surface stickiness are major determinants of high solubility and are favored in abundant bacterial proteins. Overall, our study provides a global view of aggregation rates and hence solubility limits of proteins in a bacterial cell.}, keywords = {AGGREGATION; PROTEINS; ASSOCIATION; GENE-EXPRESSION; PREDICTION; RATES; INTRINSIC DISORDER; Expression levels; INCLUSION-BODIES}, year = {2022}, eissn = {2045-2322}, orcid-numbers = {Őszi, Erika/0000-0002-0006-4683; Szappanos, Balázs/0000-0002-5075-1799} } @article{MTMT:31485019, title = {Exploring the fitness benefits of genome reduction in Escherichia coli by a selection-driven approach}, url = {https://m2.mtmt.hu/api/publication/31485019}, author = {Vernyik, Viktor and Karcagi, Ildikó and Tímár, Edit and Nagy, István and Györkei, Ádám and Papp, Balázs and Győrfy, Zsuzsanna and Pósfai, György}, doi = {10.1038/s41598-020-64074-5}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {10}, unique-id = {31485019}, issn = {2045-2322}, abstract = {Artificial simplification of bacterial genomes is thought to have the potential to yield cells with reduced complexity, enhanced genetic stability, and improved cellular economy. Of these goals, economical gains, supposedly due to the elimination of superfluous genetic material, and manifested in elevated growth parameters in selected niches, have not yet been convincingly achieved. This failure might stem from limitations of the targeted genome reduction approach that assumes full knowledge of gene functions and interactions, and allows only a limited number of reduction trajectories to interrogate. To explore the potential fitness benefits of genome reduction, we generated successive random deletions in E. coli by a novel, selection-driven, iterative streamlining process. The approach allows the exploration of multiple streamlining trajectories, and growth periods inherent in the procedure ensure selection of the fittest variants of the population. By generating single- and multiple-deletion strains and reconstructing the deletions in the parental genetic background, we showed that favourable deletions can be obtained and accumulated by the procedure. The most reduced multiple-deletion strain, obtained in five deletion cycles (2.5% genome reduction), outcompeted the wild-type, and showed elevated biomass yield. The spectrum of advantageous deletions, however, affecting only a few genomic regions, appears to be limited.}, year = {2020}, eissn = {2045-2322}, orcid-numbers = {Papp, Balázs/0000-0003-3093-8852} } @article{MTMT:31139656, title = {A génkifejeződés körkörös szabályozásától, fázisátmeneten keresztül, a genotoxikus hatások elleni védelemig}, url = {https://m2.mtmt.hu/api/publication/31139656}, author = {Györkei, Ádám and Szatmári, Orsolya and Villanyi, Zoltan}, journal-iso = {BIOKÉMIA}, journal = {BIOKÉMIA: A MAGYAR BIOKÉMIAI EGYESÜLET FOLYÓIRATA}, volume = {43}, unique-id = {31139656}, issn = {0133-8455}, year = {2019}, eissn = {2060-8152}, pages = {4-25} } @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:30644325, title = {Neutrophil count as the centerpiece in the joined association networks of inflammatory and cell damage markers, and neuroendocrine stress markers in patients with stable angina pectoris following stenting}, url = {https://m2.mtmt.hu/api/publication/30644325}, author = {Horváth, Tamás and Serfőző, Gyöngyi and Györkei, Ádám and Földesi, Imre and Forster, Tamás and Keresztes, Margit}, doi = {10.1371/journal.pone.0215209}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {14}, unique-id = {30644325}, issn = {1932-6203}, abstract = {Objective The primary aim of this study was to examine whether markers of cell damage and of the psycho-neuroendocrino-inflammatory/immune (PNI) system could be associated in patients with stable coronary artery disease (CAD) on the next day following percutaneous coronary intervention (PCI). Materials and methods Blood samples of 23 patients (18 men and five women, mean age 62.9 +/- 10.6 years), were collected immediately before (pre-PCI), immediately after (post-PCI), and on the day following PCI (1d-PCI). Lactoferrin, LL-37 and interleukin-6 (IL-6) were assayed in plasma, in addition to cortisol and chromogranin A (CgA), as well as CK, ASAT and ALAT. Total and differential leukocyte counts were also analysed. Results At all the three time points, the monocyte fractions, the monocyte-to-lymphocyte and the neutrophil-to-lymphocyte ratios and CgA levels were elevated. We detected significant peri-procedural changes in the plasma levels of our PNI markers: IL-6 (p<0.05), lactoferrin, LL-37 (both: p<0.0001), CgA, (p<0.05), and cortisol (p<0.01). On the first day after PCI, highly significant associations were found of ASAT with IL-6 and neutrophil count (both: r> 0.75, p<0.0001), and of CgA with neutrophil count and monocyte count (both: r>0.79, p<0.0001); furthermore, cortisol was also associated with neutrophil count (r>0.7, p<0.0001). Conclusions The findings suggest that myocardial damage could correlate not only with an inflammatory reaction but, via neutrophil count, also with increased level of stress in stable CAD after PCI. Furthermore, 1d-PCI neutrophil count may serve as an easy-to-obtain integrative PNI measure in stable CAD.}, keywords = {ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; percutaneous coronary intervention; Lactoferrin; ELEVATION MYOCARDIAL-INFARCTION; LONG-TERM MORTALITY; chromogranin-A; LYMPHOCYTE RATIO; ANTIMICROBIAL PEPTIDE LL-37}, year = {2019}, eissn = {1932-6203}, orcid-numbers = {Földesi, Imre/0000-0002-3329-8136; Forster, Tamás/0000-0003-3311-6475; Keresztes, Margit/0000-0001-5208-9682} } @article{MTMT:30435652, title = {Phylogenetic barriers to horizontal transfer of antimicrobial peptide resistance genes in the human gut microbiota.}, url = {https://m2.mtmt.hu/api/publication/30435652}, author = {Kintses, Bálint and Méhi, Orsolya Katinka and Ari, Eszter and Számel, Mónika and Györkei, Ádám and Jangir, Pramod Kumar and Nagy, István and Pál, Ferenc and Fekete, Gergely and Tengölics, Roland and Nyerges, Ákos and Likó, István and Bálint, Anita and Molnár, Tamás and Bálint, Balázs and Vásárhelyi, Bálint Márk and Bustamante, Misshelle and Papp, Balázs and Pál, Csaba}, doi = {10.1038/s41564-018-0313-5}, journal-iso = {NAT MICROBIOL}, journal = {NATURE MICROBIOLOGY}, volume = {4}, unique-id = {30435652}, issn = {2058-5276}, abstract = {The human gut microbiota has adapted to the presence of antimicrobial peptides (AMPs), which are ancient components of immune defence. Despite its medical importance, it has remained unclear whether AMP resistance genes in the gut microbiome are available for genetic exchange between bacterial species. Here, we show that AMP resistance and antibiotic resistance genes differ in their mobilization patterns and functional compatibilities with new bacterial hosts. First, whereas AMP resistance genes are widespread in the gut microbiome, their rate of horizontal transfer is lower than that of antibiotic resistance genes. Second, gut microbiota culturing and functional metagenomics have revealed that AMP resistance genes originating from phylogenetically distant bacteria have only a limited potential to confer resistance in Escherichia coli, an intrinsically susceptible species. Taken together, functional compatibility with the new bacterial host emerges as a key factor limiting the genetic exchange of AMP resistance genes. Finally, our results suggest that AMPs induce highly specific changes in the composition of the human microbiota, with implications for disease risks.}, year = {2019}, eissn = {2058-5276}, pages = {447-458}, orcid-numbers = {Méhi, Orsolya Katinka/0009-0004-7918-913X; Ari, Eszter/0000-0001-7774-1067; Jangir, Pramod Kumar/0000-0001-8330-0655; Pál, Ferenc/0000-0002-0985-8578; Nyerges, Ákos/0000-0002-1581-490X; Likó, István/0000-0001-7668-4726; Bálint, Anita/0000-0002-3624-896X; Molnár, Tamás/0000-0002-4913-7599; Vásárhelyi, Bálint Márk/0000-0003-1782-8691} }