{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:47:43Z","timestamp":1788857263277,"version":"build-2803163510"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32473039"],"award-info":[{"award-number":["32473039"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Natural Science Foundation of China","award":["21ZR1477000"],"award-info":[{"award-number":["21ZR1477000"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2026,1,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The type VI secretion system (T6SS) is a major virulence factor in\n                      <jats:italic toggle=\"yes\">Vibrio parahaemolyticus<\/jats:italic>\n                      , but its pathogenic mechanisms are poorly understood or still not fully understood. This study investigates how two critical T6SS1 structural components, VipA1 and Hcp1, contribute to bacterial virulence and host inflammatory responses. Comparative proteomics revealed 149 secreted proteins dependent on T6SS1, including 28 core proteins requiring both VipA1 and Hcp1 for secretion. These proteins were functionally linked to metabolic pathways such as folate-mediated one-carbon metabolism and lysine degradation, as well as structural processes like flagellar assembly. Phenotypic analysis revealed that the \u0394\n                      <jats:italic toggle=\"yes\">vipA1-hcp1<\/jats:italic>\n                      double mutant showed markedly attenuated virulence: 52.7% reduction in antibacterial activity compared to the wild-type strain. Biofilm formation increased 2.1-fold at 30\u00b0C and 2.8-fold at 37\u00b0C in \u0394\n                      <jats:italic toggle=\"yes\">vipA1-hcp1<\/jats:italic>\n                      , while swimming and swarming motility decreased by 30.9% and 35.5%.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      , \u0394\n                      <jats:italic toggle=\"yes\">vipA1-hcp1<\/jats:italic>\n                      caused only 50% mortality in mice, compared to 91.7% for the wild-type strain, and exhibited 3- to 15-fold lower bacterial loads in the blood, liver, and spleen. Histopathological analysis confirmed that the \u0394\n                      <jats:italic toggle=\"yes\">vipA1-hcp1<\/jats:italic>\n                      failed to induce tissue damage, unlike the wild-type strain. At the host interface, deletion of\n                      <jats:italic toggle=\"yes\">vipA1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">hcp1<\/jats:italic>\n                      led to significantly elevated inflammatory cytokine (IL-1\u03b2, IL-8, and IL-6) mRNA levels. Mechanistically, T6SS1 inhibited NF-\u03baB activation by stabilizing I\u03baB\u03b1 and reducing p65 nuclear translocation (40.0% in wild-type-infected cells vs 85.8% in double mutant-infected cells). These findings establish VipA1 and Hcp1 as critical regulators of T6SS1-mediated coordinating effector secretion, virulence, immune evasion, and lethality, providing novel mechanistic insights into\n                      <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                      pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00587-25","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T11:12:12Z","timestamp":1764933132000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["T6SS1 suppresses pro-inflammatory cytokine transcription to drive immune evasion and systemic infection in\n                    <i>Vibrio parahaemolyticus<\/i>"],"prefix":"10.1128","volume":"94","author":[{"given":"Shuqi","family":"Lu","sequence":"first","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese 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