{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:17:51Z","timestamp":1785439071645,"version":"3.56.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["32170199"],"award-info":[{"award-number":["32170199"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["31970179"],"award-info":[{"award-number":["31970179"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["32170177"],"award-info":[{"award-number":["32170177"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["31870130"],"award-info":[{"award-number":["31870130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["82061148018"],"award-info":[{"award-number":["82061148018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Ehrlichia chaffeensis<\/jats:italic>, a small Gram-negative obligatory intracellular bacterium, infects human monocytes or macrophages, and causes human monocytic ehrlichiosis, one of the most prevalent, life-threatening emerging zoonoses. Reactive oxygen species are produced by the host immune cells in response to bacterial infections. The mechanisms exploited by <jats:italic>E. chaffeensis<\/jats:italic> to resist oxidative stress have not been comprehensively demonstrated. Here, we found that <jats:italic>E. chaffeensis<\/jats:italic> encodes two functional enzymes, GshA and GshB, to synthesize glutathione that confers <jats:italic>E. chaffeensis<\/jats:italic> the oxidative stress resistance, and that the expression of <jats:italic>gshA<\/jats:italic> and <jats:italic>gshB<\/jats:italic> is upregulated by CtrA, a global transcriptional regulator, upon oxidative stress. We found that in <jats:italic>E. chaffeensis<\/jats:italic>, the expression of <jats:italic>gshA<\/jats:italic> and <jats:italic>gshB<\/jats:italic> was upregulated upon oxidative stress using quantitative RT-PCR. <jats:italic>Ehrlichia chaffeensis<\/jats:italic> GshA or GshB restored the ability of <jats:italic>Pseudomonas aeruginosa<\/jats:italic> GshA or GshB mutant to cope with oxidative stress, respectively. Recombinant <jats:italic>E. chaffeensis<\/jats:italic> CtrA directly bound to the promoters of <jats:italic>gshA<\/jats:italic> and <jats:italic>gshB<\/jats:italic>, determined with electrophoretic mobility shift assay, and activated the expression of <jats:italic>gshA<\/jats:italic> and <jats:italic>gshB<\/jats:italic> determined with reporter assay. Peptide nucleic acid transfection of <jats:italic>E. chaffeensis<\/jats:italic>, which reduced the CtrA protein level, inhibited the oxidative stress-induced upregulation of <jats:italic>gshA<\/jats:italic> and <jats:italic>gshB<\/jats:italic>. Our findings provide insights into the function and regulation of the two enzymes critical for <jats:italic>E. chaffeensis<\/jats:italic> resistance to oxidative stress and may deepen our understanding of <jats:italic>E. chaffeensis<\/jats:italic> pathogenesis and adaptation in hosts.<\/jats:p>","DOI":"10.3389\/fmicb.2022.846488","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T15:00:14Z","timestamp":1648652414000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiaqi","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2019an","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouyi","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1128\/iai.65.4.1455-1461.1997","article-title":"Ehrlichia chaffeensis inclusions are early endosomes which selectively accumulate transferrin receptor","volume":"65","author":"Barnewall","year":"1997","journal-title":"Infect. 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