@article{MTMT:35470389, title = {Drug combinations targeting antibiotic resistance}, url = {https://m2.mtmt.hu/api/publication/35470389}, author = {Bognár, Bence and Spohn, Réka and Lázár, Viktória}, doi = {10.1038/s44259-024-00047-2}, journal-iso = {npj Antimicrob Resist}, journal = {npj Antimicrobials and Resistance}, volume = {2}, unique-id = {35470389}, year = {2025}, eissn = {2731-8745} } @article{MTMT:35780670, title = {Exploring the principles behind antibiotics with limited resistance}, url = {https://m2.mtmt.hu/api/publication/35780670}, author = {Maharramov, Elvin and Czikkely, Márton Simon and Szili, Petra and Farkas, Zoltán and Grézal, Gábor and Daruka, Lejla and Kurkó, Eszter and Mészáros, Léna and Daraba, Andreea and Kovacs, Terezia and Bognár, Bence and Juhász, Szilvia and Papp, Balázs and Lázár, Viktória and Pál, Csaba}, doi = {10.1038/s41467-025-56934-3}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {16}, unique-id = {35780670}, abstract = {Antibiotics that target multiple cellular functions are anticipated to be less prone to bacterial resistance. Here we hypothesize that while dual targeting is crucial, it is not sufficient in preventing resistance. Only those antibiotics that simultaneously target membrane integrity and block another cellular pathway display reduced resistance development. To test the hypothesis, we focus on three antibiotic candidates, POL7306, Tridecaptin M152-P3 and SCH79797, all of which fulfill the above criteria. Here we show that resistance evolution against these antibiotics is limited in ESKAPE pathogens, including Escherichia coli , Klebsiella pneumoniae , Acinetobacter baumannii and Pseudomonas aeruginosa , while dual-target topoisomerase antibiotics are prone to resistance. We discover several mechanisms restricting resistance. First, de novo mutations result in only a limited elevation in resistance, including those affecting the molecular targets and efflux pumps. Second, resistance is inaccessible through gene amplification. Third, functional metagenomics reveal that mobile resistance genes are rare in human gut, soil and clinical microbiomes. Finally, we detect rapid eradication of bacterial populations upon toxic exposure to membrane targeting antibiotics. We conclude that resistance mechanisms commonly found in natural bacterial pathogens provide only limited protection to these antibiotics. Our work provides guidelines for the future development of antibiotics.}, year = {2025}, eissn = {2041-1723}, orcid-numbers = {Czikkely, Márton Simon/0009-0008-6123-9927; Grézal, Gábor/0000-0003-1685-4791} } @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} } @article{MTMT:34230980, title = {Predictive Potential of RNA Polymerase B (II) Subunit 1 (RPB1) Cytoplasmic Aggregation for Neoadjuvant Chemotherapy Failure}, url = {https://m2.mtmt.hu/api/publication/34230980}, author = {Nagy-Mikó, Bence and Szatmári, Orsolya and Faragó-Mészáros, Réka and Csókási, Aliz and Bognár, Bence and Ördög, Nóra and Borsos, Barbara Nikolett and Majoros, Hajnalka and Újfaludi, Zsuzsanna and Oláh, Orsolya and Nikolényi, Alíz and Dobi, Ágnes and Kószó, Renáta Lilla and Sántha, Dóra and Lázár, György ifj and Simonka, Zsolt and Paszt, Attila and Ormándi, Katalin and Pankotai, Tibor and Boros, Imre Miklós and Villanyi, Zoltan and Vörös, András}, doi = {10.3390/ijms242115869}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {34230980}, issn = {1661-6596}, abstract = {We aimed to investigate the contribution of co-translational protein aggregation to the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation reflects altered translation regulation that may have the potential to buffer transcription under genotoxic stress. As an indicator for such an event, we followed the cytoplasmic aggregation of RPB1, the aggregation-prone largest subunit of RNA polymerase II, in biopsy samples taken from patients with invasive carcinoma of no special type. RPB1 frequently aggregates co-translationally in the absence of proper HSP90 chaperone function or in ribosome mutant cells as revealed formerly in yeast. We found that cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression after therapy. Based on these results, we propose that monitoring the cytoplasmic aggregation of RPB1 may be suitable for determining—from biopsy samples taken before treatment—the effectiveness of neoadjuvant chemotherapy.}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Ördög, Nóra/0000-0003-1931-4053; Borsos, Barbara Nikolett/0000-0002-5537-8612; Majoros, Hajnalka/0000-0003-2020-971X; Újfaludi, Zsuzsanna/0000-0003-4738-0963; Oláh, Orsolya/0000-0002-5731-4030; Nikolényi, Alíz/0000-0003-4608-3158; Dobi, Ágnes/0000-0003-0445-4504; Kószó, Renáta Lilla/0000-0002-1958-7839; Lázár, György ifj/0000-0001-7155-2978; Simonka, Zsolt/0000-0002-3490-226X; Paszt, Attila/0000-0002-1637-8652; Pankotai, Tibor/0000-0001-9810-5465; Boros, Imre Miklós/0000-0001-8504-9687; Vörös, András/0000-0001-6837-0567} }