{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:45:45Z","timestamp":1792784745808,"version":"4.5.0"},"reference-count":44,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["MM4TB, Grant 260872"],"award-info":[{"award-number":["MM4TB, Grant 260872"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Institutes of Health Research (CIHR)","award":["FDN-148362"],"award-info":[{"award-number":["FDN-148362"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In patients with cystic fibrosis, nontuberculous mycobacteria are opportunistic, intracellular and extracellular pulmonary pathogens that contribute to deterioration of lung function and, ultimately, morbidity from respiratory failure. Among nontuberculous mycobacterial respiratory pathogens, members of the Mycobacterium abscessus complex pose additional treatment complications as they are notoriously drug-resistant. As part of our routine screening against mycobacterial species, one of the lead antituberculosis compounds, the cytochrome bc1 inhibitor AX-35, was found to be active against isolates from the Mycobacterium abscessus complex in vitro (MIC \u2264 15 \u03bcg\/mL) and ex vivo in infected macrophages. Isolation and characterization of AX-35-resistant mutants in M. abscessus ATCC 19977 (MIC AX-35 &amp;gt; 100 \u03bcg\/mL) revealed the presence of a chimeric gene resulting from the recombination of 737 bps of MAB_2467 into MAB_1966c. In M. abscessus, both genes encode for the b subunit of the cytochrome bc1 oxidase, also known as QcrB. Further analysis, comprising gene inactivation, ATP-depletion assays, AlphaFold3-based structural modeling, and molecular docking, suggested that the product of MAB_1966c is the target of AX-35. Interestingly, transcriptomic analysis of M. abscessus exposed to AX-35 revealed that the compound induced expression of MAB_2467 and the alternate terminal oxidase, cytochrome bd. In M. tuberculosis, in the absence of the cytochrome bd oxidase, QcrB inhibitors, including AX-35, are bactericidal. However, in M. abscessus, AX-35 had bacteriostatic activity. These results suggested that, in the presence of AX-35, MAB_2467 may compensate for the absence of the cytochrome bd oxidase and that M. abscessus ATCC 19977 genome encodes two QcrB paralogs.<\/jats:p>","DOI":"10.1021\/acsinfecdis.6c00313","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T06:02:02Z","timestamp":1790575322000},"page":"3362-3372","source":"Crossref","is-referenced-by-count":0,"title":["AX-35 Targets\nthe Cytochrome bc1 Complex\nin\n                    <i>Mycobacterium abscessus<\/i>\n                    and Reveals\na Novel Resistance Mechanism"],"prefix":"10.1021","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-0497","authenticated-orcid":true,"given":"Andre\u0301anne","family":"Lupien","sequence":"first","affiliation":[{"name":"McGill University Faculty of Medicine and Health Sciences , , 1001 boul Decarie , , ,","place":["Montreal, Quebec, Canada, H4A 3J1"]},{"name":"Research Institute of the McGill University Health Centre, Infectious Diseases and Immunity in Global Health Program , 1001 boul Decarie , , ,","place":["Montreal, Quebec, Canada, H4A3J1"]},{"name":"McGill University Faculty of Medicine and Health Sciences, Microbiology and Immunology , 3775 Rue University Room 511 , , ,","place":["Montreal, Quebec, Canada, H3A0G4"]},{"name":"Ecole Polytechnique Fe\u0301de\u0301rale de Lausanne , , ,","place":["Lausanne, Switzerland, 1015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Dessureault","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health Centre, Infectious Diseases and Immunity in Global Health Program , 1001 boul Decarie , , ,","place":["Montreal, Quebec, Canada, H4A3J1"]},{"name":"McGill University Faculty of Medicine and Health Sciences, Microbiology and Immunology , 3775 Rue University Room 511 , , ,","place":["Montreal, Quebec, Canada, H3A0G4"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Shi-Yan","family":"Foo","sequence":"additional","affiliation":[{"name":"Ecole Polytechnique Fe\u0301de\u0301rale de Lausanne , , ,","place":["Lausanne, Switzerland, 1015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryline","family":"Kienle","sequence":"additional","affiliation":[{"name":"ETH Zurich Institute of Pharmaceutical Sciences , , Vladimir-Prelog-Weg 4 , , ,","place":["Zu\u0308rich, Zu\u0308rich, Switzerland, 8093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Vocat","sequence":"additional","affiliation":[{"name":"Ecole Polytechnique Fe\u0301de\u0301rale de Lausanne , , ,","place":["Lausanne, Switzerland, 1015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Benjak","sequence":"additional","affiliation":[{"name":"Ecole Polytechnique Fe\u0301de\u0301rale de Lausanne , , ,","place":["Lausanne, Switzerland, 1015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Roe","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health Centre, Infectious Diseases and Immunity in Global Health Program , 1001 boul Decarie , , ,","place":["Montreal, Quebec, Canada, H4A3J1"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0747-9734","authenticated-orcid":true,"given":"Karl-Heinz","family":"Altmann","sequence":"additional","affiliation":[{"name":"ETH Zurich Institute of Pharmaceutical Sciences , , Vladimir-Prelog-Weg 4 , , ,","place":["Zu\u0308rich, Zu\u0308rich, Switzerland, 8093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart T.","family":"Cole","sequence":"additional","affiliation":[{"name":"Ecole Polytechnique Fe\u0301de\u0301rale de Lausanne , , ,","place":["Lausanne, Switzerland, 1015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel A.","family":"Behr","sequence":"additional","affiliation":[{"name":"McGill University Faculty of Medicine and Health Sciences , , 1001 boul Decarie , , ,","place":["Montreal, Quebec, Canada, H4A 3J1"]},{"name":"Research Institute of the McGill University Health Centre, Infectious Diseases and Immunity in Global Health Program , 1001 boul Decarie , , ,","place":["Montreal, Quebec, Canada, H4A3J1"]},{"name":"McGill University Faculty of Medicine and Health Sciences, Microbiology and Immunology , 3775 Rue University Room 511 , , ,","place":["Montreal, Quebec, Canada, H3A0G4"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"7","key":"2026100909095725600_cit1","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/s41579-020-0331-1","article-title":"Non-Tuberculous Mycobacteria and\nthe Rise of Mycobacterium Abscessus","volume":"18","author":"Johansen","year":"2020","journal-title":"Nat. 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A."},{"issue":"1","key":"2026100909095725600_cit34","doi-asserted-by":"publisher","first-page":"5370","DOI":"10.1038\/s41467-018-07804-8","article-title":"Targeting the Mycobacterium\nUlcerans Cytochrome Bc1: Aa3 for the Treatment of Buruli Ulcer","volume":"9","author":"Scherr","year":"2018","journal-title":"Nat. Commun."},{"issue":"18","key":"2026100909095725600_cit35","doi-asserted-by":"publisher","first-page":"10331","DOI":"10.3390\/ijms231810331","article-title":"Response of\nMycobacterium Smegmatis to the Cytochrome Bcc Inhibitor Q203","volume":"23","author":"Chauhan","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"2026100909095725600_cit36","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1038\/s41598-018-20989-8","article-title":"The Anti-Mycobacterial Activity of\nthe Cytochrome Bcc Inhibitor Q203 Can Be Enhanced by Small-Molecule\nInhibition of Cytochrome Bd","volume":"8","author":"Lu","year":"2018","journal-title":"Sci. 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