{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T19:23:57Z","timestamp":1771529037827,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012043","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000}}],"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI143768"],"award-info":[{"award-number":["R01 AI143768"]}],"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":["R21 AI168597"],"award-info":[{"award-number":["R21 AI168597"]}],"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":["R35 GM144282"],"award-info":[{"award-number":["R35 GM144282"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI007422"],"award-info":[{"award-number":["T32 AI007422"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Successful host colonization by bacterial pathogens requires appropriate response and adaptation to environmental signals encountered during infection, with two-component systems (TCSs) and serine\/threonine protein kinases (STPKs) being two important signal transduction mechanisms.\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) possesses similar numbers of STPKs (11) and TCSs (12), but if and how these two regulatory systems coordinate to enable Mtb adaptation in response to key environmental cues remains poorly understood. Here, we identify extensive interactions between STPKs and TCSs, with a subset of STPKs demonstrating interactions with multiple TCS response regulators. STPK phosphorylation of purified DosR, the response regulator of the key nitric oxide (NO)\/hypoxia-responsive TCS DosRS(T), decreased its binding to target promoter DNA and its ability to activate steady-state gene transcription, in marked contrast with the opposite phenotypes observed with the activated, phospho-aspartic acid form of DosR. Strikingly, a \u0394STPK Mtb mutant exhibited increased DosR regulon transcription at lower NO levels than wild type Mtb, illustrating how STPK phosphorylation of a TCS RR may act to restrict and fine-tune conditions in which activation occurs. Together, our results support a functional relationship between STPKs and TCSs, and shed light on the mechanisms underpinning STPK-TCS interplay.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012043","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T18:40:31Z","timestamp":1770921631000},"page":"e1012043","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serine\/threonine protein kinase phosphorylation of DosR alters target gene transcription mechanics and regulates Mycobacterium tuberculosis response to nitric oxide stress"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-9988","authenticated-orcid":true,"given":"Natalie R.","family":"Sontag","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9135-1436","authenticated-orcid":true,"given":"Ana","family":"Ruiz Manzano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1619-3885","authenticated-orcid":true,"given":"Alwyn M. 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