{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T06:13:08Z","timestamp":1784441588151,"version":"3.55.0"},"posted":{"date-parts":[[2025,10,24]]},"group-title":"Microbiology","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                  has emerged as a significant pulmonary pathogen characterized by its resistance to most first-line antimycobacterial drugs. Recent investigations have highlighted the clinical efficacy of including the oxazolidinone antibiotic linezolid in\n                  <jats:italic>M. abscessus<\/jats:italic>\n                  combination therapies, despite moderate resistance frequently being observed in patient isolates. Even with the potential usefulness of linezolid, the mechanisms that drive linezolid resistance in\n                  <jats:italic>M. abscessus<\/jats:italic>\n                  remain poorly understood. In several bacterial pathogens, including\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  , ATP-binding cassette (ABC) family proteins of the F subtype (ABC-F) have been found to confer antibiotic resistance to ribosome-targeting antibiotics, including linezolid. Here, we identified an\n                  <jats:italic>M. abscessus<\/jats:italic>\n                  ABC-F protein, MAB_2736c, that causes specific resistance to antibiotics that bind the 50S ribosomal subunit, including linezolid, macrolides, and chloramphenicol. These results demonstrate that targeting ABC-F proteins could help combat intrinsic resistance to several ribosome-targeting antibiotics in mycobacteria.\n                <\/jats:p>","DOI":"10.1101\/2025.10.24.684387","type":"posted-content","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T03:30:13Z","timestamp":1761363013000},"source":"Crossref","is-referenced-by-count":1,"title":["Ribosomal protection as a linezolid resistance mechanism in\n                  <i>Mycobacterium abscessus<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8660-7451","authenticated-orcid":false,"given":"Tobias","family":"Funck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8451-4070","authenticated-orcid":false,"given":"Kerry","family":"McGowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5765-0459","authenticated-orcid":false,"given":"Mark R.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Zinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian D.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Nurjadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7216-7067","authenticated-orcid":false,"given":"Claudia M.","family":"Denkinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5120-962X","authenticated-orcid":false,"given":"Eric J.","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025102804350499000_2025.10.24.684387v1.1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201804-236OC"},{"key":"2025102804350499000_2025.10.24.684387v1.2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01206-17"},{"key":"2025102804350499000_2025.10.24.684387v1.3","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01977"},{"key":"2025102804350499000_2025.10.24.684387v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr578"},{"key":"2025102804350499000_2025.10.24.684387v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.04.001"},{"issue":"2","key":"2025102804350499000_2025.10.24.684387v1.6","first-page":"e01842","article-title":"Molecular Analysis of Linezolid-Resistant Clinical Isolates of Mycobacterium abscessus","volume":"63","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"2025102804350499000_2025.10.24.684387v1.7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.diagmicrobio.2018.10.022","article-title":"Genetic mutations in linezolid-resistant Mycobacterium avium complex and Mycobacterium abscessus clinical isolates","volume":"94","year":"2019","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2025102804350499000_2025.10.24.684387v1.8","unstructured":"WHO consolidated guidelines on tuberculosis. Module 4: treatment-drug-resistant tuberculosis treatment, 2022 update [Internet]. [cited 2025 Sep 21]. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240063129"},{"key":"2025102804350499000_2025.10.24.684387v1.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2119430"},{"key":"2025102804350499000_2025.10.24.684387v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2022.105734"},{"key":"2025102804350499000_2025.10.24.684387v1.11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.073626"},{"issue":"3","key":"2025102804350499000_2025.10.24.684387v1.12","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1021\/acsinfecdis.7b00251","article-title":"Antibiotic Resistance ABC-F Proteins: Bringing Target Protection into the Limelight","volume":"4","year":"2018","journal-title":"ACS Infect Dis"},{"key":"2025102804350499000_2025.10.24.684387v1.13","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01975-15"},{"key":"2025102804350499000_2025.10.24.684387v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29274-9"},{"issue":"7","key":"2025102804350499000_2025.10.24.684387v1.15","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1093\/nar\/gky050","article-title":"Antibiotic resistance ABCF proteins reset the peptidyl transferase centre of the ribosome to counter translational arrest","volume":"46","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"2025102804350499000_2025.10.24.684387v1.16","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/s41579-020-0386-z","article-title":"Target protection as a key antibiotic resistance mechanism","volume":"18","year":"2020","journal-title":"Nat Rev Microbiol"},{"issue":"4","key":"2025102804350499000_2025.10.24.684387v1.17","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/pro.3589","article-title":"Ribosome protection by ABC-F proteins-Molecular mechanism and potential drug design","volume":"28","year":"2019","journal-title":"Protein Sci Publ Protein Soc"},{"key":"2025102804350499000_2025.10.24.684387v1.18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808535115"},{"key":"2025102804350499000_2025.10.24.684387v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23753-1"},{"key":"2025102804350499000_2025.10.24.684387v1.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1803313115"},{"key":"2025102804350499000_2025.10.24.684387v1.21","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01184-21"},{"key":"2025102804350499000_2025.10.24.684387v1.22","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv116"},{"issue":"12","key":"2025102804350499000_2025.10.24.684387v1.23","first-page":"1095","article-title":"Enterococcal isolates carrying the novel oxazolidinone resistance gene optrA from hospitals in Zhejiang, Guangdong, and Henan, China, 2010\u20132014","volume":"21","year":"2015","journal-title":"Clin Microbiol Infect"},{"key":"2025102804350499000_2025.10.24.684387v1.24","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx292"},{"key":"2025102804350499000_2025.10.24.684387v1.25","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jgar.2017.05.002","article-title":"Detection of the optrA gene in a clinical ST16 Enterococcus faecalis isolate in Denmark","volume":"10","year":"2017","journal-title":"J Glob Antimicrob Resist"},{"key":"2025102804350499000_2025.10.24.684387v1.26","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00188-20"},{"key":"2025102804350499000_2025.10.24.684387v1.27","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky088"},{"issue":"6","key":"2025102804350499000_2025.10.24.684387v1.28","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/s41564-022-01130-y","article-title":"CRISPRi chemical genetics and comparative genomics identify genes mediating drug potency in Mycobacterium tuberculosis","volume":"7","year":"2022","journal-title":"Nat Microbiol"},{"key":"2025102804350499000_2025.10.24.684387v1.29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1112"},{"issue":"1","key":"2025102804350499000_2025.10.24.684387v1.30","first-page":"8","article-title":"The MycoBrowser portal: a comprehensive and manually annotated resource for mycobacterial genomes","volume":"91","year":"2011","journal-title":"Tuberc Edinb Scotl"},{"key":"2025102804350499000_2025.10.24.684387v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-021-03819-2"},{"key":"2025102804350499000_2025.10.24.684387v1.32","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.71947"},{"issue":"4","key":"2025102804350499000_2025.10.24.684387v1.33","first-page":"1","article-title":"Programmable transcriptional repression in mycobacteria using an orthogonal CRISPR interference platform","volume":"2","year":"2017","journal-title":"Nat Microbiol"},{"issue":"18","key":"2025102804350499000_2025.10.24.684387v1.34","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1016\/j.jmb.2018.12.013","article-title":"ABCF ATPases Involved in Protein Synthesis, Ribosome Assembly and Antibiotic Resistance: Structural and Functional Diversification across the Tree of Life","volume":"431","year":"2019","journal-title":"J Mol Biol"},{"key":"2025102804350499000_2025.10.24.684387v1.35","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2217\/fmb-2018-0207","article-title":"Mycobacterium tuberculosis Rv1473 is a novel macrolides ABC Efflux Pump regulated by WhiB7","volume":"14","year":"2019","journal-title":"Future Microbiol"},{"key":"2025102804350499000_2025.10.24.684387v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/90802"},{"key":"2025102804350499000_2025.10.24.684387v1.37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005010"},{"key":"2025102804350499000_2025.10.24.684387v1.38","unstructured":"PyMOL | pymol.org [Internet]. [cited 2024 Apr 10]. Available from: https:\/\/pymol.org\/"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.10.24.684387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:08:37Z","timestamp":1782277717000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.10.24.684387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":38,"URL":"https:\/\/doi.org\/10.1101\/2025.10.24.684387","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1128\/aac.01605-25","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,10,24]]},"subtype":"preprint"}}