{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T14:50:57Z","timestamp":1784213457206,"version":"3.55.0"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006377","name":"Purdue University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006377","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015083","name":"Department of Biological Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015083","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Mycobacterium abscessus<\/jats:italic> is a biofilm-forming, non-tuberculous mycobacterium that is highly resistant to antibiotics. Bacterial efflux pumps contribute to biofilm formation, export of biofilm-associated lipids and antibiotic tolerance. The Resistance Nodulation Cell Division (RND) and ATP-Binding Cassette (ABC) families of efflux pumps export lipids to the mycobacterial cell surface. 1-(1-naphthyl methyl)-piperazine (NMP) is a chemosensitizer that causes membrane destabilization and is an inhibitor of RND efflux pumps. The effects of NMP on biofilm formation and lipid metabolism in <jats:italic>M<\/jats:italic>. <jats:italic>abscessus<\/jats:italic> biofilms have not been investigated. Plumbagin (PLU) is an inhibitor of ABC efflux pumps that has not been studied for its effects on antibiotic tolerance in <jats:italic>M<\/jats:italic>. <jats:italic>abscessus<\/jats:italic> biofilms. In this study, we report that the efflux pump inhibitors NMP and PLU inhibit biofilm formation by 50% at sub-MIC levels. We show that NMP inhibits the incorporation of the radiolabeled long-chain fatty acid <jats:sup>14<\/jats:sup>C-palmitate into glycopeptidolipids in cell surface lipids of log-phase <jats:italic>M<\/jats:italic>. <jats:italic>abscessus<\/jats:italic>. NMP also inhibits the utilization of the radiolabel in the biosynthesis of phosphatidylethanolamine in the cell surface and cellular lipids of <jats:italic>M<\/jats:italic>. <jats:italic>abscessus<\/jats:italic> cells in log-phase and in biofilms. Incorporation of the radiolabel into cardiolipin in the cellular lipids of <jats:italic>M<\/jats:italic>. <jats:italic>abscessus<\/jats:italic> biofilms was inhibited by NMP. The incorporation of <jats:sup>14<\/jats:sup>C-acetate into cell surface phosphatidylethanolamine in log-phase and biofilm cells was also inhibited by NMP. Triacylglycerol biosynthesis using <jats:sup>14<\/jats:sup>C-palmitate and <jats:sup>14<\/jats:sup>C-acetate in cellular lipids of log-phase and biofilm cells was increased several folds by NMP. Efflux pump activity in <jats:italic>M<\/jats:italic>. <jats:italic>abscessus<\/jats:italic> cells was inhibited by 97% and 68% by NMP and PLU respectively. NMP and PLU caused 5-fold decreases in the minimum inhibitory concentrations of ciprofloxacin and clarithromycin against <jats:italic>M<\/jats:italic>. <jats:italic>abscessus<\/jats:italic>. Our results demonstrate that NMP and PLU affect important physiological processes in <jats:italic>M<\/jats:italic>. <jats:italic>abscessus<\/jats:italic> associated with its pathogenesis.<\/jats:p>","DOI":"10.1371\/journal.pone.0311669","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T18:32:34Z","timestamp":1731436354000},"page":"e0311669","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Biofilm formation and polar lipid biosynthesis in Mycobacterium abscessus are inhibited by naphthylmethylpiperazine"],"prefix":"10.1371","volume":"19","author":[{"given":"Timilehin","family":"Faboro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3605-687X","authenticated-orcid":true,"given":"Jaiyanth","family":"Daniel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"issue":"7","key":"pone.0311669.ref001","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41579-020-0331-1","article-title":"Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus","volume":"18","author":"MD Johansen","year":"2020","journal-title":"Nat Rev Microbiol"},{"issue":"11","key":"pone.0311669.ref002","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1080\/17476348.2023.2283135","article-title":"A narrative review of nontuberculous mycobacterial pulmonary disease: microbiology, epidemiology, diagnosis, and management challenges.","volume":"17","author":"KA Hamed","year":"2023","journal-title":"Expert Rev Respir Med."},{"issue":"4","key":"pone.0311669.ref003","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/mmi.13482","article-title":"MAB_3551c encodes the primary triacylglycerol synthase involved in lipid accumulation in Mycobacterium abscessus","volume":"102","author":"A Viljoen","year":"2016","journal-title":"Mol Microbiol"},{"issue":"6","key":"pone.0311669.ref004","doi-asserted-by":"crossref","first-page":"e1002093","DOI":"10.1371\/journal.ppat.1002093","article-title":"Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages","volume":"7","author":"J Daniel","year":"2011","journal-title":"PLoS Pathog"},{"issue":"11","key":"pone.0311669.ref005","doi-asserted-by":"crossref","first-page":"e1000204","DOI":"10.1371\/journal.ppat.1000204","article-title":"Foamy macrophages from tuberculous patients\u2019 granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence","volume":"4","author":"P Peyron","year":"2008","journal-title":"PLoS Pathog"},{"issue":"7","key":"pone.0311669.ref006","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/emmm.201000079","article-title":"Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism","volume":"2","author":"MJ Kim","year":"2010","journal-title":"EMBO Mol Med"},{"issue":"2 Pt 1","key":"pone.0311669.ref007","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1164\/ajrccm.154.2.8756832","article-title":"Nontuberculous mycobacteria in cystic fibrosis. 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