{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:15:05Z","timestamp":1788372905950,"version":"build-2803163510"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI155473"],"award-info":[{"award-number":["AI155473"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI187284"],"award-info":[{"award-number":["AI187284"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32GM132066"],"award-info":[{"award-number":["T32GM132066"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    A major determinant of the exceptional intrinsic resistance of M. abscessus is the lipid-rich cell envelope, yet the regulatory systems that remodel envelope-associated pathways remain poorly defined. Here, we determine the \u03c3\n                    <jats:sup>D<\/jats:sup>\n                    regulon in\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    and establish its role in cell envelope homeostasis and intrinsic resistance to hydrophobic antibiotics. RNA-Seq analysis of a Mab\u0394\n                    <jats:italic>sigD<\/jats:italic>\n                    mutant identified 447 differentially expressed genes, while ChIP-Seq mapped 72 \u03c3\n                    <jats:sup>D<\/jats:sup>\n                    binding sites and defined a conserved promoter motif (GTAACA\/G-N\n                    <jats:sub>16<\/jats:sub>\n                    -CGAT). Using a combination of \u03c3\n                    <jats:sup>D<\/jats:sup>\n                    binding, motif orientation and expression data, we identified a core set of directly regulated genes, distinct from what was previously observed in\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    , many of which encode proteins involved in envelope-associated functions. These include loci involved in trehalose polyphleate (TPP) biosynthesis, the antigen 85 complex and peptidoglycan remodeling enzymes. Deletion of\n                    <jats:italic>sigD<\/jats:italic>\n                    resulted in a significant reduction in TPPs in the cell envelope and an increase in ethidium bromide accumulation. Consistent with these changes, loss of \u03c3\n                    <jats:sup>D<\/jats:sup>\n                    selectively sensitized\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    to hydrophobic antibiotics, including rifampicin and tigecycline. Deletion of\n                    <jats:italic>mmpL10<\/jats:italic>\n                    , which is required for transport of TPP precursors, recapitulated the drug sensitivity of Mab\u0394\n                    <jats:italic>sigD<\/jats:italic>\n                    , implicating envelope composition as a key effector of the phenotype. Expression of the \u03c3\n                    <jats:sup>D<\/jats:sup>\n                    regulon further increased during starvation and in response to SDS, isoniazid, and ethambutol, mediated by degradation of RsdA, consistent with a role in stress-responsive envelope adaptation. Together, these findings demonstrate \u03c3\n                    <jats:sup>D<\/jats:sup>\n                    is active during logarithmic growth in rich media where it regulates the expression of envelope-associated genes that influence envelope permeability and basal level susceptibility to hydrophobic antibiotics; its activity further increases in response to cell envelope stress, presumably promoting envelope remodeling to counteract damage.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012286","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:33:03Z","timestamp":1788370383000},"page":"e1012286","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["The SigD regulon of Mycobacterium abscessus determines cell envelope composition and antibiotic susceptibility"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9384-6455","authenticated-orcid":true,"given":"Sean R.","family":"Jones","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4699-1220","authenticated-orcid":true,"given":"Kelly","family":"Maune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley","family":"Hurst-Hess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1622-7301","authenticated-orcid":true,"given":"Pallavi","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"issue":"6","key":"pgen.1012286.ref001","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1164\/rccm.200207-678OC","article-title":"Nontuberculous mycobacteria. 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