{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:35:41Z","timestamp":1789130141035,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Aerobic respiration is the key driver of <jats:italic>Vibrio cholerae<\/jats:italic> proliferation and infection.\u00a0Our previous transcriptome results suggested that <jats:italic>degS<\/jats:italic> knockout downregulates a few genes involved in NADH and ATP synthesis in the aerobic respiratory pathway. In this study, non-targeted metabolomics results showed that the differential metabolites affected by <jats:italic>degS<\/jats:italic> knockout were associated with aerobic respiration. Further results suggested that the key products of aerobic respiration, NADH and ATP, were reduced upon <jats:italic>degS<\/jats:italic> deletion and were not dependent on the classical \u03c3<jats:sup>E<\/jats:sup> pathway. The two-component system response factor aerobic respiration control A (ArcA) is involved in regulating NADH and ATP levels. qRT-PCR demonstrated that DegS negatively regulates the transcription of the <jats:italic>arcA<\/jats:italic> gene, which negatively regulates the expression of isocitrate dehydrogenase (ICDH), a key rate-limiting enzyme of the tricarboxylic acid cycle. NADH and ATP levels were partially restored with the knockout of the <jats:italic>arcA<\/jats:italic> gene in the <jats:italic>\u0394degS<\/jats:italic> strain, while levels were partially restored with overexpression of ICDH in the <jats:italic>\u0394degS<\/jats:italic> strain. In a growth experiment, compared to the <jats:italic>\u0394degS<\/jats:italic> strain, the growth rates of <jats:italic>\u0394degS\u0394arcA<\/jats:italic> and <jats:italic>\u0394degS<\/jats:italic>-overexpressed <jats:italic>icdh<\/jats:italic> strains (<jats:italic>\u0394degS+icdh<\/jats:italic>) were partially restored during the logarithmic growth period. Colonization of the intestines of suckling mice showed a significant reduction in the colonizing ability of the <jats:italic>\u0394degS<\/jats:italic> strain, similar colonizing ability of the <jats:italic>\u0394degS::degS<\/jats:italic> strain and the wild-type strain, and a partial recovery of the colonizing ability of the <jats:italic>\u0394degS<\/jats:italic>+<jats:italic>icdh<\/jats:italic> strain. Overall, these findings suggest that the DegS protease regulates the expression of ICDH through ArcA, thereby affecting the NADH and ATP levels of <jats:italic>V. cholerae<\/jats:italic> and its growth and intestinal colonization ability.<\/jats:p>","DOI":"10.3389\/fcimb.2024.1482919","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T06:11:20Z","timestamp":1730441480000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["DegS regulates the aerobic metabolism of Vibrio cholerae via the ArcA-isocitrate dehydrogenase pathway for growth and intestinal colonization"],"prefix":"10.3389","volume":"14","author":[{"given":"Jiajun","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanqin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1101\/gad.13.18.2449","article-title":"The Escherichia coli sigma(E)-dependent extracytoplasmic stress response is controlled by the regulated proteolysis of an anti-sigma factor","volume":"13","author":"Ades","year":"1999","journal-title":"Genes Dev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"11866","DOI":"10.1038\/s41598-017-12144-6","article-title":"ArcA overexpression induces fermentation and results in enhanced growth rates of E. coli","volume":"7","author":"Basan","year":"2017","journal-title":"Sci. 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