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Recent genomic studies have identified several virulence-associated genes (VAGs), including\n                    <jats:italic>SSU_RS09155<\/jats:italic>\n                    ,\n                    <jats:italic>SSU_RS09525<\/jats:italic>\n                    , and\n                    <jats:italic>SSU_RS03100<\/jats:italic>\n                    , as potential markers of pathogenicity. The current study evaluated the direct contribution of these genes to\n                    <jats:italic>S. suis<\/jats:italic>\n                    virulence using isogenic deletion mutants of the serotype 2 reference strain P1\/7. In a murine infection model,\n                    <jats:italic>\u0394SSU_RS09525<\/jats:italic>\n                    and\n                    <jats:italic>\u0394SSU_RS03100<\/jats:italic>\n                    mutants displayed virulence comparable to the parental strain, whereas the\n                    <jats:italic>\u0394SSU_RS09155<\/jats:italic>\n                    mutant was significantly attenuated, showing reduced mortality and bacteremia. In\u00a0vitro, the\n                    <jats:italic>\u0394SSU_RS09155<\/jats:italic>\n                    mutant demonstrated increased susceptibility to killing in whole blood and enhanced phagocytosis by murine macrophages, while no significant defects in capsular polysaccharide (CPS) expression or growth in rich medium and mouse and porcine plasma were observed. Complementation restored the resistance to the whole-blood killing phenotype, confirming the specific role of\n                    <jats:italic>SSU_RS09155<\/jats:italic>\n                    . Adhesion to and invasion of porcine tracheal epithelial cells were unaffected. In pigs, the natural host, the\n                    <jats:italic>\u0394SSU_RS09155<\/jats:italic>\n                    mutant was almost completely avirulent, with minimal to undetectable bacteremia. In\u00a0silico analysis suggested that\n                    <jats:italic>SSU_RS09155<\/jats:italic>\n                    encodes a hydrophobic, membrane-associated protein potentially involved in resistance to innate immune mechanisms, although the real function remains unknown. Together, these findings identify\n                    <jats:italic>SSU_RS09155<\/jats:italic>\n                    as a critical virulence factor in\n                    <jats:italic>S. suis<\/jats:italic>\n                    serotype 2, whereas\n                    <jats:italic>SSU_RS09525<\/jats:italic>\n                    and\n                    <jats:italic>SSU_RS03100<\/jats:italic>\n                    appear dispensable under the experimental conditions tested.\n                  <\/jats:p>","DOI":"10.1186\/s13567-026-01761-7","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T09:13:53Z","timestamp":1777972433000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SSU_RS09155, a virulence-associated gene encoding a putative membrane of unknown function, that is essential for Streptococcus suis serotype 2 virulence"],"prefix":"10.1186","volume":"57","author":[{"given":"Servane","family":"Payen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Lacouture","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahuel","family":"Fittipaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela","family":"Segura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Gottschalk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"1761_CR1","unstructured":"Gottschalk M, Segura M, Costa M (2025) Streptococcocis. 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