{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:03:50Z","timestamp":1785290630846,"version":"3.55.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFD1800400"],"award-info":[{"award-number":["2021YFD1800400"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31872480"],"award-info":[{"award-number":["31872480"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31973004"],"award-info":[{"award-number":["31973004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007540","name":"Jiangsu Agriculture Science and Technology Innovation Fund","doi-asserted-by":"crossref","award":["CX(19)2020"],"award-info":[{"award-number":["CX(19)2020"]}],"id":[{"id":"10.13039\/100007540","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["PAPD"],"award-info":[{"award-number":["PAPD"]}],"id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>GntR transcription factor of <jats:italic>Streptococcus suis<\/jats:italic> serotype 2 (SS2) is a potential substrate protein of STK, but the regulation mechanisms of GntR phosphorylation are still unclear. This study confirmed that STK phosphorylated GntR <jats:italic>in vivo<\/jats:italic>, and <jats:italic>in vitro<\/jats:italic> phosphorylation experiments showed that STK phosphorylated GntR at Ser-41. The phosphomimetic strain (GntR-S41E) had significantly reduced lethality in mice and reduced bacterial load in the blood, lung, liver, spleen, and brain of infected mice compared to wild-type (WT) SS2. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments demonstrated that the promoter of <jats:italic>nox<\/jats:italic> was bound by GntR. The phosphomimetic protein GntR-S41E cannot bind to the promoter of <jats:italic>nox<\/jats:italic>, and the <jats:italic>nox<\/jats:italic> transcription levels were significantly reduced in the GntR-S41E mutant compared to WT SS2. The virulence in mice and the ability to resist oxidative stress of the GntR-S41E strain were restored by complementing transcript levels of <jats:italic>nox<\/jats:italic>. NOX is an NADH oxidase that catalyzes the oxidation of NADH to NAD<jats:sup>+<\/jats:sup> with the reduction of oxygen to water. We found that NADH is likely accumulated under oxidative stress in the GntR-S41E strain, and higher NADH levels resulted in increased amplified ROS killing. In total, we report GntR phosphorylation could inhibit the transcription of <jats:italic>nox<\/jats:italic>, which impaired the ability of SS2 to resist oxidative stress and virulence.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011227","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T17:23:19Z","timestamp":1678728199000},"page":"e1011227","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Phosphorylation of GntR reduces Streptococcus suis oxidative stress resistance and virulence by inhibiting NADH oxidase transcription"],"prefix":"10.1371","volume":"19","author":[{"given":"Kai","family":"Niu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixing","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5212-5759","authenticated-orcid":true,"given":"Hongjie","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"issue":"7","key":"ppat.1011227.ref001","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.tim.2017.02.005","article-title":"Critical Streptococcus suis Virulence Factors: Are They All Really Critical?","volume":"25","author":"M Segura","year":"2017","journal-title":"Trends in microbiology"},{"issue":"7","key":"ppat.1011227.ref002","first-page":"e01712","article-title":"Pathotyping the Zoonotic Pathogen Streptococcus suis: Novel Genetic Markers To Differentiate Invasive Disease-Associated Isolates from Non-Disease-Associated Isolates from England and Wales","volume":"57","author":"M Wileman Thomas","journal-title":"Journal of Clinical Microbiology"},{"issue":"9","key":"ppat.1011227.ref003","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens9090707","article-title":"Streptococcus suis Research: Progress and Challenges","volume":"9","author":"M. 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