{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T02:44:18Z","timestamp":1773369858127,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32160833"],"award-info":[{"award-number":["32160833"]}],"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":["32160834"],"award-info":[{"award-number":["32160834"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"XPCC \u201cRevitalizing Villages","award":["2024YD026-05"],"award-info":[{"award-number":["2024YD026-05"]}]},{"name":"Eighth Division, Shihezi City Technology-Commissioned Project \u201cExtension of Efficient & Healthy Livestock and Poultry Farming Technologies","award":["0110302051"],"award-info":[{"award-number":["0110302051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Listeria monocytogenes (Lm) is a foodborne pathogen whose virulence depends on the coordinated action of multiple virulence factors. Although deletion of either LIPI-4 or inlB reduces the virulence of Listeria monocytogenes, it remains unknown whether these two factors are functionally or regulatory connected. Therefore, we constructed an inlB deletion mutant and its complemented strain in the Lm928 and \u0394LIPI-4 backgrounds. We assessed bacterial growth, biofilm formation, motility, host cell interactions (adhesion, invasion, intracellular proliferation), plaque formation, mouse organ colonization. Growth curve analysis showed no significant differences among strains. qPCR revealed that LIPI-4 modulates inlB expression in a cell-type-specific manner: inlB was downregulated in \u0394LIPI-4 under culture and HTR-8 infection, but upregulated during hCMEC\/D3 infection\u2014yet functional defects persisted in all cases. Biofilm assays showed that \u0394LIPI-4 and the double mutant exhibited enhanced biofilm formation, with the double mutant exceeding \u0394LIPI-4, demonstrating synergistic enhancement. Motility assays indicated that LIPI-4 dominates bacterial movement, with \u0394LIPI-4 and the double mutant showing identical severe defects. Plaque formation analysis showed that LIPI-4 is essential for cell-to-cell spread, while inlB deletion unexpectedly enhanced plaque formation\u2014an effect completely abolished in the absence of LIPI-4. Host cell assays across Caco-2, HTR-8, and hCMEC\/D3 models revealed that LIPI-4 is the core determinant of adhesion, invasion, and intracellular proliferation, whereas inlB contributes in the context of LIPI-4 and its effects vary with the specific cellular process examined. In mice, LIPI-4 was essential for systemic colonization of the liver and spleen, with inlB acting as a co-factor, whereas inlB unexpectedly promoted higher bacterial burdens in the brain, suggesting that inlB modulates LIPI-4-mediated neuroinvasion. Overall, our results establish LIPI-4 as the central determinant of Lm virulence, with inlB acting as a context-dependent co-factor that modulates LIPI-4-mediated pathogenesis in a cell type- and tissue-specific manner.<\/jats:p>","DOI":"10.3390\/microorganisms14030645","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:46:31Z","timestamp":1773326791000},"page":"645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LIPI-4 as a Critical Modulator of InlB-Mediated Pathogenicity in Listeria monocytogenes"],"prefix":"10.3390","volume":"14","author":[{"given":"Yatao","family":"Qi","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Xinjiang Academy of Agricultural Reclamation Sciences, Shihezi 832000, China"},{"name":"National Key Laboratory of Genetic Improvement and Healthy Sheep Breeding, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3778-1539","authenticated-orcid":false,"given":"Caixia","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruixuan","family":"Qian","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5293-2279","authenticated-orcid":false,"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongke","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"001800","DOI":"10.1099\/jmm.0.001800","article-title":"Listeria monocytogenes: The Silent Assassin: This Article Is Part of the JMM Profiles Collection","volume":"73","author":"Fotopoulou","year":"2024","journal-title":"J. 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