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This study investigated 315\n                    <jats:italic>S. suis<\/jats:italic>\n                    isolates collected from clinically healthy pigs in Guangdong and Guangxi provinces between 2024 and 2025. Among these isolates, 34 capsular polysaccharide (\n                    <jats:italic>cps<\/jats:italic>\n                    ) types were identified, with 40.63% belonging to\n                    <jats:italic>cps<\/jats:italic>\n                    types associated with human infections. The isolates exhibited high genetic diversity, distributed across 80 sequence types (STs), 13 clonal complexes (CCs), and five minimum core genomes (MCGs). Animal infection models demonstrated that a considerable proportion of healthy-pig-derived strains displayed high virulence in zebrafish and mouse models. Cytotoxicity assays confirmed that isolates belonging to CC1, CC7, CC17, CC94, and CC108 caused significant cytotoxicity toward A549 and hBMEC cells. Alarmingly, 96.82% of the isolates were multidrug-resistant, and notably, 29.84% showed resistance to penicillin. Furthermore, various integrative and conjugative elements (ICEs) and prophages were identified in these strains. Homology analysis revealed that ICEs carried by highly virulent healthy-pig-derived strains shared high similarity with those from highly virulent human-derived strains and even human-derived\n                    <jats:italic>Streptococcus agalactiae<\/jats:italic>\n                    , raising concerns about the possible dissemination of virulence-associated determinants via ICEs. This study highlights the emergence of multidrug-resistant and highly virulent\n                    <jats:italic>S. suis<\/jats:italic>\n                    strains in healthy pig populations. The dual threat of pathogenicity and antimicrobial resistance, coupled with the horizontal gene transfer capacity of ICEs and prophages, constitutes a serious public health risk, underscoring the urgent need for enhanced surveillance.\n                  <\/jats:p>","DOI":"10.1186\/s13567-026-01832-9","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T16:54:58Z","timestamp":1788022498000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidrug-resistant and virulent Streptococcus suis strains detected in clinically healthy pigs in Guangdong and Guangxi, China"],"prefix":"10.1186","volume":"57","author":[{"given":"Zeren","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongkun","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Quereda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6048-6829","authenticated-orcid":false,"given":"Zongfu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"issue":"7","key":"1832_CR1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.tim.2017.02.005","volume":"25","author":"M Segura","year":"2017","unstructured":"Segura M, Fittipaldi N, Calzas C, Gottschalk M (2017) Critical Streptococcus suis virulence factors: are they all really critical? 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