{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:29:08Z","timestamp":1788499748947,"version":"build-2803163510"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"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":["U22A20534"],"award-info":[{"award-number":["U22A20534"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hainan Provincial Natural Science Foundation of China","award":["326JCQN0967"],"award-info":[{"award-number":["326JCQN0967"]}]},{"name":"Innovational Fund for Scientific and Technological Personnel of Hainan Province","award":["KJRC2023B22"],"award-info":[{"award-number":["KJRC2023B22"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Type I interferons (IFNs) are indispensable antiviral cytokines in nonspecific immunity, yet they play dual roles in bacterial infections in mammals. Recent studies have revealed a subset of strongly cationic type I IFNs possessing potent antimicrobial properties across nonmammalian vertebrates. In this study, we identified a type I IFN gene,\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi, from\n                    <jats:italic>Cromileptes altivelis<\/jats:italic>\n                    that is characterized by a unique triple-disulfide bond architecture. In\n                    <jats:italic>Vibrio harveyi<\/jats:italic>\n                    -challenged models, overexpression of\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi potentiated bacterial clearance capacity in tissues, whereas its knockdown exacerbated bacterial colonization, highlighting its ability to protect the host against bacterial infection\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                    <jats:italic>In vitro<\/jats:italic>\n                    assays further confirmed that\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi directly binds to and kills both gram-negative (G\n                    <jats:sup>-<\/jats:sup>\n                    ) and gram-positive (G\n                    <jats:sup>+<\/jats:sup>\n                    ) bacteria, which first revealed the antibacterial function of new subgroup IFNi within teleost type I IFNs. Furthermore, the \u03b1-helical peptide\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi-18 derived from\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi was identified as a novel antimicrobial peptide (AMP) that has broad-spectrum antibacterial efficacy against G\n                    <jats:sup>-<\/jats:sup>\n                    and G\n                    <jats:sup>+<\/jats:sup>\n                    bacteria and membrane-targeting ability. Further mechanistic studies revealed that\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi has bactericidal effects on both G\n                    <jats:sup>-<\/jats:sup>\n                    and G\n                    <jats:sup>+<\/jats:sup>\n                    bacteria through membrane depolarization and disruption, alteration of the bacterial ultrastructure, and\n                    <jats:italic>in vitro<\/jats:italic>\n                    binding to genomic DNA. In addition,\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi-18 also has significant\n                    <jats:italic>in vivo<\/jats:italic>\n                    therapeutic efficacy against bacterial infection, highlighting its great potential as an antibacterial agent. Encouragingly, the loss of antibacterial activity in the truncation mutant (r\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi\u0394148-165) lacking the\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi-18 segment suggests that this region is essential for the bactericidal function of the full-length protein and likely acts as its core domain. Further computational simulations revealed that the deletion of the\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi-18 region attenuated the interaction between the protein and the bacterial membrane. These findings not only expand the functional scope of type I IFNs beyond their canonical antiviral role but also identify their derivative\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi-18 as both a promising antimicrobial candidate and the essential bactericidal domain of\n                    <jats:italic>Ca<\/jats:italic>\n                    IFNi, thereby offering novel therapeutic strategies against bacterial infections in the aquaculture industry and beyond.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014419","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:33:43Z","timestamp":1785260023000},"page":"e1014419","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Noncanonical bactericidal activity of teleost type I interferon is conferred by a membrane-targeting C-terminal peptide"],"prefix":"10.1371","volume":"22","author":[{"given":"Han","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjie","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqun","family":"Ao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongcan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-7208","authenticated-orcid":true,"given":"Yun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"issue":"11","key":"ppat.1014419.ref001","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1007\/s11427-022-2112-0","article-title":"The 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