@article{MTMT:34014839, title = {Effects of bowel cleansing on the composition of the gut microbiota in inflammatory bowel disease patients and healthy controls}, url = {https://m2.mtmt.hu/api/publication/34014839}, author = {Bacsur, Péter and Rutka, Mariann and Asbóth, András and Resál, Tamás and Szántó, Kata Judit and Jójárt, Boldizsár and Bálint, Anita and Ari, Eszter and Ajibola, Walliyulahi and Kintses, Bálint and Fehér, Tamás and Pigniczki , Daniella and Bor, Renáta and Fábián, Anna and Maléth, József and Szepes, Zoltán and Farkas, Klaudia and Molnár, Tamás}, doi = {10.1177/17562848231174298}, journal-iso = {THER ADV GASTROENTER}, journal = {THERAPEUTIC ADVANCES IN GASTROENTEROLOGY}, volume = {16}, unique-id = {34014839}, issn = {1756-283X}, year = {2023}, eissn = {1756-2848}, orcid-numbers = {Bacsur, Péter/0000-0002-8534-0068; Rutka, Mariann/0000-0003-2360-7836; Resál, Tamás/0000-0002-3842-9094; Szántó, Kata Judit/0000-0003-0749-5061; Jójárt, Boldizsár/0000-0002-2764-3925; Bálint, Anita/0000-0002-3624-896X; Ari, Eszter/0000-0001-7774-1067; Fehér, Tamás/0000-0001-9318-3640; Pigniczki , Daniella/0000-0001-6395-2576; Bor, Renáta/0000-0001-9393-5240; Fábián, Anna/0000-0002-0824-7476; Maléth, József/0000-0001-5768-3090; Szepes, Zoltán/0000-0002-9466-8719; Farkas, Klaudia/0000-0003-0599-182X; Molnár, Tamás/0000-0002-4913-7599} } @article{MTMT:33634821, title = {Characterization of antibiotic resistomes by reprogrammed bacteriophage-enabled functional metagenomics in clinical strains}, url = {https://m2.mtmt.hu/api/publication/33634821}, author = {Apjok, Gábor and Számel, Mónika and Christodoulou, Chryso and Seregi, Viktória and Vásárhelyi, Bálint Márk and Stirling, Tamás and Eszenyi, Bálint Dénes and Sári , Tóbiás and Vidovics, Fanni and Nagrand, Erika and Kovács, Dorina and Szili, Petra and Lantos, Ildikó Ilona and Méhi, Orsolya Katinka and Jangir, Pramod Kumar and Herczeg, Róbert and Gálik, Bence and Urbán, Péter and Gyenesei, Attila and Draskovits, Gábor and Nyerges, Ákos and Fekete, Gergely and Bodai, László and Zsindely, Nóra and Dénes, Béla and Yosef, Ido and Qimron, Udi and Papp, Balázs and Pál, Csaba and Kintses, Bálint}, doi = {10.1038/s41564-023-01320-2}, journal-iso = {NAT MICROBIOL}, journal = {NATURE MICROBIOLOGY}, volume = {8}, unique-id = {33634821}, issn = {2058-5276}, abstract = {Functional metagenomics is a powerful experimental tool to identify antibiotic resistance genes (ARGs) in the environment, but the range of suitable host bacterial species is limited. This limitation affects both the scope of the identified ARGs and the interpretation of their clinical relevance. Here we present a functional metagenomics pipeline called Reprogrammed Bacteriophage Particle Assisted Multi-species Functional Metagenomics (DEEPMINE). This approach combines and improves the use of T7 bacteriophage with exchanged tail fibres and targeted mutagenesis to expand phage host-specificity and efficiency for functional metagenomics. These modified phage particles were used to introduce large metagenomic plasmid libraries into clinically relevant bacterial pathogens. By screening for ARGs in soil and gut microbiomes and clinical genomes against 13 antibiotics, we demonstrate that this approach substantially expands the list of identified ARGs. Many ARGs have species-specific effects on resistance; they provide a high level of resistance in one bacterial species but yield very limited resistance in a related species. Finally, we identified mobile ARGs against antibiotics that are currently under clinical development or have recently been approved. Overall, DEEPMINE expands the functional metagenomics toolbox for studying microbial communities.}, year = {2023}, eissn = {2058-5276}, pages = {410-423}, orcid-numbers = {Apjok, Gábor/0000-0002-8627-2378; Vásárhelyi, Bálint Márk/0000-0003-1782-8691; Stirling, Tamás/0000-0002-8964-6443; Méhi, Orsolya Katinka/0009-0004-7918-913X; Jangir, Pramod Kumar/0000-0001-8330-0655; Herczeg, Róbert/0000-0002-5903-0082; Gálik, Bence/0000-0002-3949-7005; Nyerges, Ákos/0000-0002-1581-490X; Bodai, László/0000-0001-8411-626X; Zsindely, Nóra/0000-0002-6189-3100; Dénes, Béla/0000-0002-9889-529X} } @article{MTMT:33040340, title = {A Single Early Introduction Governed Viral Diversity in the Second Wave of SARS-CoV-2 Epidemic in Hungary}, url = {https://m2.mtmt.hu/api/publication/33040340}, author = {Ari, Eszter and Vásárhelyi, Bálint Márk and Kemenesi, Gábor and Tóth, Gábor Endre and Zana, Brigitta and Somogyi, Balázs Antal and Lanszki, Zsófia and Röst, Gergely and Jakab, Ferenc and Papp, Balázs and Kintses, Bálint}, doi = {10.1093/ve/veac069}, journal-iso = {VIRUS EVOL}, journal = {VIRUS EVOLUTION}, volume = {8}, unique-id = {33040340}, abstract = {Retrospective evaluation of past waves of the SARS-CoV-2 epidemic is key for designing optimal interventions against future waves and novel pandemics. Here we report on analysing genome sequences of SARS-CoV-2 from the first two waves of the epidemic in 2020 in Hungary, mirroring a suppression and a mitigation strategy, respectively. Our analysis reveals that the two waves markedly differed in viral diversity and transmission patterns. Specifically, unlike in several European areas or in the USA, we have found no evidence for early introduction and cryptic transmission of the virus in the first wave of the pandemic in Hungary. Despite the introduction of multiple viral lineages, extensive community spread was prevented by a timely national lockdown in March 2020. In sharp contrast, the majority of the cases in the much larger second wave can be linked to a single transmission lineage of the pan-European B.1.160 variant. This lineage was introduced unexpectedly early, followed by a two-month-long cryptic transmission before a soar of detected cases in September 2020. Epidemic analysis has revealed that the dominance of this lineage in the second wave was not associated with an intrinsic transmission advantage. This finding is further supported by the rapid replacement of B.1.160 by the alpha variant (B.1.1.7) that launched the third wave of the epidemic in February 2021. Overall, these results illustrate how the founder effect in combination with cryptic transmission, instead of repeated international introductions or higher transmissibility, can govern viral diversity.}, year = {2022}, eissn = {2057-1577}, orcid-numbers = {Ari, Eszter/0000-0001-7774-1067; Vásárhelyi, Bálint Márk/0000-0003-1782-8691; Kemenesi, Gábor/0000-0001-9775-3065; Tóth, Gábor Endre/0000-0002-7201-9646; Lanszki, Zsófia/0000-0003-3116-4633; Röst, Gergely/0000-0001-9476-3284} } @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} } @misc{MTMT:32476999, title = {A COVID-19 PANDÉMIÁHOZ TÁRSULÓAN ELŐFORDULT MULTIREZISZTENS ACINETOBACTER BAUMANNII TÖRZSEK MOLEKULÁRIS JELLEMZÉSE}, url = {https://m2.mtmt.hu/api/publication/32476999}, author = {Visnyovszki, Ádám and Orosz, László and Kintses, Bálint and Stirling, Tamás and Vásárhelyi, Bálint Márk and Ari, Eszter and Kiss, Enikő and Papp, Balázs and Apjok, Gábor and Vidovics, Fanni and Lakatos, Lóránt and Lengyel, György and Ánosi, Noel and Sóki, József and Baaity, Zain and Hajdú, Edit and Burián, Katalin}, unique-id = {32476999}, year = {2021}, orcid-numbers = {Stirling, Tamás/0000-0002-8964-6443; Vásárhelyi, Bálint Márk/0000-0003-1782-8691; Ari, Eszter/0000-0001-7774-1067; Lengyel, György/0000-0002-0534-5935; Sóki, József/0000-0001-9230-8907; Baaity, Zain/0000-0001-6411-382X; Burián, Katalin/0000-0003-1300-2374} } @article{MTMT:31720772, title = {Suboptimal global transcriptional response increases the harmful effects of loss-of-function mutations}, url = {https://m2.mtmt.hu/api/publication/31720772}, author = {Kovács, Károly and Farkas, Zoltán and Bajić, Djordje and Kalapis, Dorottya and Daraba, Andreea and Almási, Karola and Kintses, Bálint and Bódi, Zoltán and Notebaart, Richard A and Poyatos, Juan F and Kemmeren, Patrick and Holstege, Frank C P and Pál, Csaba and Papp, Balázs}, doi = {10.1093/molbev/msaa280}, journal-iso = {MOL BIOL EVOL}, journal = {MOLECULAR BIOLOGY AND EVOLUTION}, volume = {38}, unique-id = {31720772}, issn = {0737-4038}, year = {2021}, eissn = {1537-1719}, pages = {1137-1150} } @article{MTMT:31647953, title = {Functional Anatomical Changes in Ulcerative Colitis Patients Determine Their Gut Microbiota Composition and Consequently the Possible Treatment Outcome}, url = {https://m2.mtmt.hu/api/publication/31647953}, author = {Bálint, Anita and Farkas, Klaudia and Méhi, Orsolya Katinka and Kintses, Bálint and Vásárhelyi, Bálint Márk and Ari, Eszter and Pál, Csaba and Madácsy, Tamara and Maléth, József and Szántó, Kata Judit and Nagy, István and Rutka, Mariann and Bacsur, Péter and Szűcs, Diána and Szepes, Zoltán and Nagy, Ferenc and Fábián, Anna and Bor, Renáta and Milassin, Ágnes and Molnár, Tamás}, doi = {10.3390/ph13110346}, journal-iso = {PHARMACEUTICALS-BASE}, journal = {PHARMACEUTICALS}, volume = {13}, unique-id = {31647953}, year = {2020}, eissn = {1424-8247}, orcid-numbers = {Bálint, Anita/0000-0002-3624-896X; Farkas, Klaudia/0000-0003-0599-182X; Méhi, Orsolya Katinka/0009-0004-7918-913X; Vásárhelyi, Bálint Márk/0000-0003-1782-8691; Ari, Eszter/0000-0001-7774-1067; Madácsy, Tamara/0000-0001-5598-9723; Maléth, József/0000-0001-5768-3090; Szántó, Kata Judit/0000-0003-0749-5061; Rutka, Mariann/0000-0003-2360-7836; Bacsur, Péter/0000-0002-8534-0068; Szepes, Zoltán/0000-0002-9466-8719; Fábián, Anna/0000-0002-0824-7476; Bor, Renáta/0000-0001-9393-5240; Milassin, Ágnes/0000-0001-6902-8915; Molnár, Tamás/0000-0002-4913-7599} } @article{MTMT:31642956, title = {Rational design of balanced dual-targeting antibiotics with limited resistance}, url = {https://m2.mtmt.hu/api/publication/31642956}, author = {Nyerges, Ákos and Tomasic, Tihomir and Durcik, Martina and Révész, Tamás and Szili, Petra and Draskovits, Gábor and Bogár, Ferenc and Skok, Ziga and Zidar, Nace and Ilas, Janez and Zega, Anamarija and Kikelj, Danijel and Daruka, Lejla and Kintses, Bálint and Vásárhelyi, Bálint Márk and Földesi, Imre and Kata, Diána and Welin, Martin and Kimbung, Raymond and Focht, Dorota and Masic, Lucija Peterlin and Pál, Csaba}, doi = {10.1371/journal.pbio.3000819}, journal-iso = {PLOS BIOL}, journal = {PLOS BIOLOGY}, volume = {18}, unique-id = {31642956}, issn = {1544-9173}, abstract = {Antibiotics that inhibit multiple bacterial targets offer a promising therapeutic strategy against resistance evolution, but developing such antibiotics is challenging. Here we demonstrate that a rational design of balanced multitargeting antibiotics is feasible by using a medicinal chemistry workflow. The resultant lead compounds, ULD1 and ULD2, belonging to a novel chemical class, almost equipotently inhibit bacterial DNA gyrase and topoisomerase IV complexes and interact with multiple evolutionary conserved amino acids in the ATP-binding pockets of their target proteins. ULD1 and ULD2 are excellently potent against a broad range of gram-positive bacteria. Notably, the efficacy of these compounds was tested against a broad panel of multidrug-resistantStaphylococcus aureusclinical strains. Antibiotics with clinical relevance against staphylococcal infections fail to inhibit a significant fraction of these isolates, whereas both ULD1 and ULD2 inhibit all of them (minimum inhibitory concentration [MIC] <= 1 mu g/mL). Resistance mutations against these compounds are rare, have limited impact on compound susceptibility, and substantially reduce bacterial growth. Based on their efficacy and lack of toxicity demonstrated in murine infection models, these compounds could translate into new therapies against multidrug-resistant bacterial infections.}, year = {2020}, eissn = {1545-7885}, orcid-numbers = {Nyerges, Ákos/0000-0002-1581-490X; Tomasic, Tihomir/0000-0001-5534-209X; Bogár, Ferenc/0000-0002-0611-1452; Vásárhelyi, Bálint Márk/0000-0003-1782-8691; Földesi, Imre/0000-0002-3329-8136; Kata, Diána/0000-0002-4432-9380; Focht, Dorota/0000-0003-3373-7335} } @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} }