{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:59:46Z","timestamp":1790348386875,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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>\n                    <jats:italic>Edwardsiella piscicida<\/jats:italic>\n                    is a devastating bacterial pathogen in aquaculture, and in-depth elucidation of its pathogenic mechanisms is essential for establishing effective control strategies; the identification of novel regulatory factors can deepen our understanding of bacterial pathogenesis. Our previous work identified the functionally uncharacterized protein ETAE_2516 as a potential target of the response regulator CpxR of the CpxRA two-component system, a key virulence regulator in this pathogen. Bioinformatic analysis and functional prediction indicated that ETAE_2516 is an AraC-family transcription factor that is potentially involved in glycerol metabolism; it was therefore designated GlvR (Glycerol-linked Virulence Regulator). In this study, an in-frame\n                    <jats:italic>glvR<\/jats:italic>\n                    deletion mutant (\u0394\n                    <jats:italic>glvR<\/jats:italic>\n                    ) and its complemented strain (\u0394\n                    <jats:italic>glvR<\/jats:italic>\n                    C) were constructed by gene knockout, and their phenotypes in metabolism, stress resistance, biofilm formation, and pathogenicity were systematically characterized. Deletion of\n                    <jats:italic>glvR<\/jats:italic>\n                    did not affect basal bacterial growth but significantly increased sensitivity to oxidative stress and led to intracellular accumulation of reactive oxygen species. The \u0394\n                    <jats:italic>glvR<\/jats:italic>\n                    mutant exhibited markedly impaired growth in glycerol-supplemented medium, and the expression of glycerol metabolism-associated genes was significantly downregulated, confirming that GlvR positively regulates glycerol metabolism. Loss of GlvR also repressed the expression of\n                    <jats:italic>flhC<\/jats:italic>\n                    , the master regulator of the flagellar regulon, thereby impairing bacterial motility. Infection assays using tilapia epithelial (TSE-04) cells, RAW 264.7 macrophages, and a tilapia (\n                    <jats:italic>Oreochromis niloticus<\/jats:italic>\n                    ) infection model demonstrated that GlvR is essential for bacterial adhesion to host epithelial cells, resistance to host serum killing, intracellular survival within macrophages, and tissue colonization, and all of these defects were restored to wild-type levels in the complemented strain, verifying that they are specifically attributable to the loss of\n                    <jats:italic>glvR<\/jats:italic>\n                    . Analysis of the upstream regulatory mechanism further revealed that CpxR binds directly to the\n                    <jats:italic>glvR<\/jats:italic>\n                    promoter region and positively activates its transcription. Collectively, these findings demonstrate that the CpxR\u2013GlvR regulatory axis functions as a central hub integrating carbon metabolism, oxidative stress adaptation, and virulence expression, thereby providing a novel perspective for understanding the host adaptation mechanisms of\n                    <jats:italic>E. piscicida<\/jats:italic>\n                    and a potential target for anti-virulence strategies against edwardsiellosis.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1963223","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:13:42Z","timestamp":1790345622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The CpxR\u2013GlvR regulatory axis of Edwardsiella piscicida: a novel virulence regulatory mechanism integrating glycerol metabolism and oxidative stress adaptation"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiancheng","family":"Jiang","sequence":"first","affiliation":[{"name":"College of Fisheries, Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjie","family":"Gu","sequence":"additional","affiliation":[{"name":"Institute of Tropical Bioscience and Biotechnology & Sanya Research Institute, Chinese Academy of Tropical Agricultural Sciences","place":["Haikou, China"]},{"name":"Zhanjiang Experimental Station, Chinese Academy of Tropical Agricultural Sciences","place":["Zhanjiang, China"]},{"name":"Hainan Provincial Key Laboratory for Functional Components Research and Utilization of Marine Bio-resources","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Tropical Bioscience and Biotechnology & Sanya Research Institute, Chinese Academy of Tropical Agricultural Sciences","place":["Haikou, China"]},{"name":"Zhanjiang Experimental Station, Chinese Academy of Tropical Agricultural Sciences","place":["Zhanjiang, China"]},{"name":"Hainan Provincial Key Laboratory for Functional Components Research and Utilization of Marine Bio-resources","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Tropical Bioscience and Biotechnology & Sanya Research Institute, Chinese Academy of Tropical Agricultural Sciences","place":["Haikou, China"]},{"name":"Zhanjiang Experimental Station, Chinese Academy of Tropical Agricultural Sciences","place":["Zhanjiang, China"]},{"name":"Hainan Provincial Key Laboratory for Functional Components Research and Utilization of Marine Bio-resources","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Fisheries, Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjian","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Tropical Bioscience and Biotechnology & Sanya Research Institute, Chinese Academy of Tropical Agricultural Sciences","place":["Haikou, China"]},{"name":"Hainan Provincial Key Laboratory for Functional Components Research and Utilization of Marine Bio-resources","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1093\/femsre\/fux033","article-title":"Glycerol metabolism and its implication in virulence in Mycoplasma","volume":"41","author":"Bl\u00f6tz","year":"2017","journal-title":"FEMS Microbiol. 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