{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:45:17Z","timestamp":1791261917250,"version":"4.1.0"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Mycobacterium abscessus<\/jats:italic> (<jats:italic>Mab<\/jats:italic>), an emerging opportunistic pathogen, predominantly infects individuals with underlying pulmonary diseases such as cystic fibrosis (CF). Current treatment outcomes for <jats:italic>Mab<\/jats:italic> infections are poor due to <jats:italic>Mab\u2019s<\/jats:italic> inherent antibiotic resistance and unique host interactions that promote phenotypic tolerance and hinder drug access. The hypoxic, mucus-laden airways in the CF lung and antimicrobial phagosome within macrophages represent hostile niches <jats:italic>Mab<\/jats:italic> must overcome <jats:italic>via<\/jats:italic> alterations in gene expression for survival. Regulatory mechanisms important for the adaptation and long-term persistence of <jats:italic>Mab<\/jats:italic> within the host are poorly understood, warranting further genetic and transcriptomics study of this emerging pathogen. DosRS<jats:italic><jats:sub>Mab<\/jats:sub><\/jats:italic>, a two-component signaling system (TCS), is one proposed mechanism utilized to subvert host defenses and counteract environmental stress such as hypoxia. The homologous TCS of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>), DosRS<jats:italic><jats:sub>Mtb<\/jats:sub><\/jats:italic>, is known to induce a ~50 gene regulon in response to hypoxia, carbon monoxide (CO) and nitric oxide (NO) <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Previously, a small DosR<jats:italic><jats:sub>Mab<\/jats:sub><\/jats:italic> regulon was predicted using bioinformatics based on DosR<jats:italic><jats:sub>Mtb<\/jats:sub><\/jats:italic> motifs however, the role and regulon of DosRS<jats:italic><jats:sub>Mab<\/jats:sub><\/jats:italic> in <jats:italic>Mab<\/jats:italic> pathogenesis have yet to be characterized in depth. To address this knowledge gap, our lab generated a <jats:italic>Mab dosRS<\/jats:italic> knockout strain (<jats:italic>Mab<jats:sub>\u0394dosRS<\/jats:sub>)<\/jats:italic> to investigate differential gene expression, and phenotype in an <jats:italic>in vitro<\/jats:italic> hypoxia model of dormancy. qRT-PCR and lux reporter assays demonstrate <jats:italic>Mab_dosR<\/jats:italic> and 6 predicted downstream genes are induced in hypoxia. In addition, RNAseq revealed induction of a much larger hypoxia response comprised of &amp;gt;1000 genes, including 127 differentially expressed genes in a <jats:italic>dosRS<\/jats:italic> mutant strain. Deletion of DosRS<jats:italic><jats:sub>Mab<\/jats:sub><\/jats:italic> led to attenuated growth under low oxygen conditions, a shift in morphotype from smooth to rough, and down-regulation of 216 genes. This study provides the first look at the global transcriptomic response of <jats:italic>Mab<\/jats:italic> to low oxygen conditions encountered in the airways of CF patients and within macrophage phagosomes. Our data also demonstrate the importance of DosRS<jats:italic><jats:sub>Mab<\/jats:sub><\/jats:italic> for adaptation of <jats:italic>Mab<\/jats:italic> to hypoxia, highlighting a distinct regulon (compared to <jats:italic>Mtb)<\/jats:italic> that is significantly larger than previously described, including both genes conserved across mycobacteria as well as <jats:italic>Mab<\/jats:italic>-specific genes.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1144210","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T09:11:31Z","timestamp":1678439491000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Mycobacterium abscessus DosRS two-component system controls a species-specific regulon required for adaptation to hypoxia"],"prefix":"10.3389","volume":"13","author":[{"given":"Breven S.","family":"Simcox","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke R.","family":"Tomlinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey N.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle H.","family":"Rohde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17665","DOI":"10.1038\/s41598-017-17751-x","article-title":"The transcriptome of mycobacterium tuberculosis in a lipid-rich dormancy model through RNAseq analysis","volume":"7","author":"Aguilar-Ayala","year":"2017","journal-title":"Sci. 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