{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:04:50Z","timestamp":1780639490098,"version":"3.54.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI181948-01"],"award-info":[{"award-number":["R01AI181948-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R21AI135173-01"],"award-info":[{"award-number":["1R21AI135173-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1RO1GM144372-01"],"award-info":[{"award-number":["1RO1GM144372-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Tuberc."],"abstract":"<jats:p>\n                    Mycobacteria encode as many as five distinct Type VII (ESX) secretion systems that function in nutrient acquisition, cell-cell interaction, membrane integrity and pathogenesis. The biological activities of ESX systems are determined by the effector proteins they secrete. ESX-4 is the ancestral secretion system and is conserved throughout mycobacteria, including\n                    <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                    where it has been shown to support survival in phagosomes. ESX-4 and putative effector genes in\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    and\n                    <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                    are co-induced by a conserved sigma factor, SigM. Identifying the activities conferred by ESX-4 in promoting\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    survival begins with identifying potential secreted substrates. We hypothesized that, in\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    , SigM co-regulates the expression of genes encoding ESX-4 components and secreted effector proteins. We generated a precise deletion of the\n                    <jats:italic>sigM<\/jats:italic>\n                    -\n                    <jats:italic>rsmA<\/jats:italic>\n                    locus, encoding SigM and its dedicated anti-sigma factor. Performing RNA-seq using this deletion strain and a SigM-expressing complementation derivative, we identified SigM-responsive mRNAs in\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    . Analysis of responsive promoters defined a consensus SigM-binding site, indicating direct induction by SigM. Together these data defined 15 SigM-targeted loci transcribing 50 genes with annotations and structures consistent with ESX secretion. While SigM induces multiple\n                    <jats:italic>esx4<\/jats:italic>\n                    locus promoters in\n                    <jats:italic>M. smegmatis<\/jats:italic>\n                    , only the promoter encoding the primary EsxU\/EsxT secreted substrates are direct targets in\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    , suggesting that production of the secretion apparatus is controlled by other transcription factors. The putative effector complexes identified here present strong candidates for the pathogenic roles previously reported for ESX-4 in\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    infection models.\n                  <\/jats:p>","DOI":"10.3389\/ftubr.2026.1797268","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:40:50Z","timestamp":1780638050000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sigma factor M induces an ESX-4-focused regulon in Mycobacterium abscessus"],"prefix":"10.3389","volume":"4","author":[{"given":"Jill G.","family":"Canestrari","sequence":"first","affiliation":[{"name":"Division of Genetics, Wadsworth Center, New York State Department of Health","place":["Albany, NY, United 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