{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:01:49Z","timestamp":1791615709769,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T00:00:00Z","timestamp":1455840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic>Mycobacterium tuberculosis<\/jats:italic> uses the Type VII ESX secretion systems to transport proteins across its complex cell wall. ESX\u20105 has been implicated in <jats:italic>M. tuberculosis<\/jats:italic> virulence, but the regulatory mechanisms controlling ESX\u20105 secretion were unknown. Here we uncover a link between ESX\u20105 and the Pst\/SenX3\u2013RegX3 system that controls gene expression in response to phosphate availability. The DNA\u2010binding response regulator RegX3 is normally activated by phosphate limitation. Deletion of <jats:italic>pstA1<\/jats:italic>, which encodes a Pst phosphate uptake system component, causes constitutive activation of RegX3. A \u0394<jats:italic>pstA1<\/jats:italic> mutant exhibited RegX3\u2013dependent overexpression of <jats:italic>esx\u20105<\/jats:italic> genes and hyper\u2010secretion of the ESX\u20105 substrates EsxN and PPE41 when the bacteria were grown in phosphate\u2010rich medium. In wild\u2010type <jats:italic>M. tuberculosis<\/jats:italic>, phosphate limitation activated <jats:italic>esx\u20105<\/jats:italic> transcription and secretion of both EsxN and PPE41, and this response required RegX3. Electrophoretic mobility shift assays revealed that RegX3 binds directly to a promoter within the <jats:italic>esx\u20105<\/jats:italic> locus. Remarkably, phosphate limitation also induced secretion of EsxB, an effector of the virulence\u2010associated ESX\u20101 secretion system, though this induction was RegX3 independent. Our work demonstrates that the Pst\/SenX3\u2013RegX3 system directly regulates ESX\u20105 secretion at the transcriptional level in response to phosphate availability and defines phosphate limitation as an environmental signal that activates ESX\u20105 secretion.<\/jats:p>","DOI":"10.1111\/mmi.13332","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T14:13:09Z","timestamp":1453471989000},"page":"510-526","source":"Crossref","is-referenced-by-count":59,"title":["Phosphate starvation: a novel signal that triggers ESX\u20105 secretion in <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1111","volume":"100","author":[{"given":"Sarah R.","family":"Elliott","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Minneapolis MN 55455 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna D.","family":"Tischler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology 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