{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:14:55Z","timestamp":1789496095527,"version":"build-2803163510"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32202992"],"award-info":[{"award-number":["32202992"]}],"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":["U23A20254"],"award-info":[{"award-number":["U23A20254"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Edwardsiella piscicida<\/jats:italic>\n                    PPD130\/91 is an important pathogen that infects both fish and humans. Upon infection,\n                    <jats:italic>E. piscicida<\/jats:italic>\n                    induces strong inflammatory responses through its type III secretion system (T3SS). The underlying mechanisms remain to be defined. Here, we demonstrate that\n                    <jats:italic>E. piscicida<\/jats:italic>\n                    T3SS effector EseJ activates the NF-\u03baB pathway in macrophages, leading to increased transcription and secretion of multiple pro-inflammatory cytokines (e.g., IL-1\u03b2 and IL-6). EseJ orchestrates NF-\u03baB signaling by interfering with two ubiquitin-dependent mechanisms that are mediated by separate functional domains of EseJ. EseJ binds to the NF-\u03baB subunit p65 via its N-terminal region of amino acids 1\u2013242, preventing the K48-linked polyubiquitination of p65 and its subsequent degradation by the proteasome. This maintains elevated levels of total and phosphorylated p65 (p-p65), facilitating p65 nuclear translocation and enhancing its transcriptional activity. EseJ also interacts with TAK1 and TRAF6 (both are upstream of the NF-\u03baB signaling pathway) via its central domain (aa 243\u2013532), thereby promoting the formation of a stable TRAF6-TAK1 complex. This interaction increases the TRAF6-dependent K27-linked polyubiquitination of TAK1, driving TAK1 phosphorylation and the subsequent activation of the IKK-I\u03baB-NF-\u03baB cascade. Inhibiting TAK1 abrogates this signaling, confirming the essential role of TAK1 in EseJ-induced NF-\u03baB activation.\n                    <jats:italic>In vivo<\/jats:italic>\n                    studies using zebrafish larvae also demonstrated that EseJ is required for\n                    <jats:italic>E. piscicida<\/jats:italic>\n                    to induce the production of pro-inflammatory cytokines. Together, we provide evidence that EseJ targets both TAK1 and p65 to promote NF-\u03baB-dependent inflammatory responses. Given the similarities among EseJ homologues in other bacteria, our finding may reveal a conserved effector-mediated immune signaling across diverse Gram-negative pathogens.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014260","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:54:18Z","timestamp":1789494858000},"page":"e1014260","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Edwardsiella T3SS effector EseJ enhances NF-\u03baB signaling by stabilizing p65 and promoting TAK1 phosphorylation"],"prefix":"10.1371","volume":"22","author":[{"given":"Tian Tian","family":"He","sequence":"first","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences","place":["Wuhan, China"]},{"name":"State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu Yu","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences","place":["Wuhan, China"]},{"name":"Universityof Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian Ru","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences","place":["Wuhan, China"]},{"name":"Universityof Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Nie","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Bing","family":"Yu","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Immunology, University of Kansas Medical Centre","place":["Kansas, Missouri, United States of America"],"department":["Department of Microbiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-5545","authenticated-orcid":true,"given":"Hai Xia","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"issue":"2","key":"ppat.1014260.ref001","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1365-2761.2006.00685.x","article-title":"Pathology of Edwardsiella tarda infection in turbot, Scophthalmus 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