{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:52:32Z","timestamp":1783569152342,"version":"3.55.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019939","name":"General Administration of Customs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019939","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Pasteurella multocida<\/jats:italic> is a pathogenic bacterium known to cause hemorrhagic septicemia and pneumonia in poultry. Reports have indicated that certain proteins, either directly involved in or regulating iron metabolism, are important virulence factors of <jats:italic>P. multocida<\/jats:italic>. Therefore, understanding virulent factors and analyzing the role of pro-inflammatory cytokines can help us elucidate the underlying pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, the PMCNA_RS00975 protein, a putative encapsuling protein encoded by a gene from a specific prophage island of the pathogenic strain <jats:italic>C48-1<\/jats:italic> of <jats:italic>P. multocida<\/jats:italic>, was investigated. To further explore the impact of the PMCNA_RS00975 protein on pathogenicity, a <jats:italic>PMCNA_RS00975<\/jats:italic> gene mutant of <jats:italic>P. multocida<\/jats:italic> strain <jats:italic>C48-1<\/jats:italic> was constructed using positive selection technology. Subcellular localization was performed to determine the location of the PMCNA_RS00975 protein within <jats:italic>P. multocida.<\/jats:italic> The recombinant protein PMCNA_RS00975 of <jats:italic>P. multocida<\/jats:italic> was soluble expressed, purified, and its role in pro-inflammatory cytokines was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mutant exhibited significantly reduced pathogenicity in the mice model. Furthermore, subcellular localization indicated that the PMCNA_RS00975 protein was located at the outer membrane and expressed during infection of <jats:italic>P. multocida.<\/jats:italic> Additionally, our experiments revealed that recombinant PMCNA_RS00975 protein promotes the secretion of the IL-6 pro-inflammatory cytokines triggered by the TLR2 receptor via NF-\u03baB and ERK1\/2 signaling pathways in the macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study identified a novel virulence factor in the <jats:italic>C48-1<\/jats:italic> strain, providing a basis for understanding the pathogenesis and directions for the development of attenuated vaccines against <jats:italic>P. multocida.<\/jats:italic><\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1469304","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T05:10:31Z","timestamp":1728969031000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["PMCNA_RS00975 activates NF-\u03baB and ERK1\/2 through TLR2 and contributes to the virulence of Pasteurella multocida"],"prefix":"10.3389","volume":"14","author":[{"given":"Tenglin","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxing","family":"Kou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peili","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiasen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfa","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongchun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liandong","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2023.106282","article-title":"Formalin and ferric chloride inactivated Pasteurella multocida type a adjuvanted with bacterial DNA and alum as a new vaccine candidate in sheep pasteurellosis","volume":"183","author":"Abbasi","year":"2023","journal-title":"Microb. 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