{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:03:15Z","timestamp":1753891395663,"version":"3.41.2"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2023YFD1800701"],"award-info":[{"award-number":["2023YFD1800701"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Salmonellosis caused by <jats:italic>Salmonella<\/jats:italic> sp. is a foodborne zoonotic disease that poses a significant threat to public health security. Vaccination is a safe and effective strategy for preventing and controlling <jats:italic>Salmonella<\/jats:italic> infections. PipC is a chaperone protein associated with <jats:italic>Salmonella<\/jats:italic> invasion proteins which is crucial for bacteria to invade host cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, a \u0394<jats:italic>pipC<\/jats:italic> mutant strain was generated. Subsequently, we examined the environmental stress tolerance of the mutant strain through <jats:italic>in vitro<\/jats:italic> simulation experiments. Moreover, its virulence by employing cell and mouse infection models was investigated. Furthermore, we utilized a mouse model to further explore its potential as an attenuated live vaccine against <jats:italic>Salmonella enterica<\/jats:italic> serovar <jats:italic>Enteritidis<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:italic>Salmonella<\/jats:italic> strain C50336 with a deletion of the <jats:italic>pipC<\/jats:italic> gene exhibits a significant reduction in its ability to resist environmental stress and virulence. Meanwhile, the expression levels of SPI-1-related genes (<jats:italic>invH<\/jats:italic>, <jats:italic>sipA<\/jats:italic>, <jats:italic>sipB<\/jats:italic>, <jats:italic>sipC<\/jats:italic>, <jats:italic>sopB<\/jats:italic>, and <jats:italic>sopE2<\/jats:italic>) and SPI-2-related genes (<jats:italic>spvB<\/jats:italic>, <jats:italic>ssrA<\/jats:italic>, <jats:italic>orf245<\/jats:italic>, <jats:italic>ssaS<\/jats:italic>, <jats:italic>ssaT<\/jats:italic>, <jats:italic>ssaU<\/jats:italic>, <jats:italic>sseB<\/jats:italic>, and <jats:italic>sseD<\/jats:italic>) encoding the <jats:italic>Salmonella<\/jats:italic> type III secretion system (T3SS) were found to be decreased, leading to a significant reduction in the bacteria\u2019s invasion and intracellular survival abilities. The results of the mouse intraperitoneal challenge experiment showed that compared with the wild-type strain, the 50% lethal dose (LD<jats:sub>50<\/jats:sub>) of the \u0394<jats:italic>pipC<\/jats:italic> strain increased by 47 times, and the bacterial loads in the liver, spleen, and cecum were significantly reduced. When mice were immunized with the \u0394<jats:italic>pipC<\/jats:italic> mutant strain, the immunized mice showed a robust immune response, with significantly increased cytokine and antibody levels in their bodies. Mice vaccinated with the \u0394<jats:italic>pipC<\/jats:italic> mutant strain had 100% immune protection against wild-type <jats:italic>Salmonella<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates that lack of <jats:italic>pipC<\/jats:italic> affects <jats:italic>SE<\/jats:italic> pathogenicity by decreasing its virulence both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Vaccination of mice with \u0394<jats:italic>pipC<\/jats:italic> conferred development of an acquired immunity and efficacious protection against experimental systemic infection. These results indicated that the \u0394<jats:italic>pipC<\/jats:italic> mutant strain can be used in the development of attenuated live vaccines.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1631008","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T05:21:47Z","timestamp":1750742507000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PipC affects the virulence of Salmonella enterica serovar Enteritidis and its deletion strain provides effective immune protection in mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Lu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuntai","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiumei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tonglei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e0259334","DOI":"10.1371\/journal.pone.0259334","article-title":"Salmonella chitosan nanoparticle vaccine administration is protective against Salmonella Enteritidis in broiler birds","volume":"16","author":"Acevedo-Villanueva","year":"2021","journal-title":"PLoS One"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2424983","DOI":"10.1080\/19490976.2024.2424983","article-title":"Immunogenicity and cross-protective efficacy induced by delayed attenuated Salmonella with regulated length of lipopolysaccharide in mice","volume":"16","author":"Bian","year":"2024","journal-title":"Gut Microbes"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1038\/s41598-022-24150-4","article-title":"Geography shapes the genomics and antimicrobial resistance of Salmonella enterica serovar Enteritidis isolated from humans","volume":"13","author":"Cao","year":"2023","journal-title":"Sci. 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