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It can be classified into more than 3000 sequence types (STs), among which the ST1 and ST123 lineages are highly prevalent in Spain. ST1 is a globally distributed lineage, while ST123 has emerged within the last decade only in Spain. In this study, we compared the genotypic and phenotypic characteristics of representative isolates from both lineages to better understand the factors driving the emergence of ST123. Comparative genomic analysis revealed higher genetic variability in ST123 than in ST1. The genomes of both lineages share approximately 1429 genes, representing about 61% of the total genome. Among the lineage-specific genes, we identified 131\u2013143  genes encoding proteins involved in diverse biological functions, including metabolism, regulation, transport, and virulence. Some of these genes were located on genetic islands, encoding for proteins involved in\u00a0nutrition and catabolism of specific carbohydrates. In mouse infection models, both STs showed a strong capacity to cause systemic infection, although they differed in tissue persistence patterns. In macrophage cultures, ST123 isolates showed reduced adherence and intracellular survival compared with ST1. In contrast, ST123 isolates demonstrated the capacity to acquire ampicillin resistance under laboratory conditions. Moreover, ST123 isolates exhibited increased biofilm formation and enhanced tolerance to \u03b2-lactam antibiotics within biofilms compared with ST1. In conclusion, the combination of virulence, increased biofilm-associated antibiotic tolerance, and increased\u00a0 propensity to acquire\u00a0 antimicrobial resistance may explain the rising prevalence of ST123 in Spain. Its recent detection in Italy further supports its potential for expansion and establishment across Europe in the coming years.\n                  <\/jats:p>","DOI":"10.1186\/s13567-026-01782-2","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:18:56Z","timestamp":1781245136000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinically relevant genomic and phenotypic differences in virulence, antimicrobial resistance, and biofilm-associated tolerance between Streptococcus suis lineages ST1 and ST123"],"prefix":"10.1186","volume":"57","author":[{"given":"Cristina","family":"Uru\u00e9n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara M.","family":"Mar\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Daniel","family":"Gonz\u00e1lez-V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Gottschalk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Arenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Arenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"1782_CR1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.medmal.2017.10.001","volume":"48","author":"B Haas","year":"2018","unstructured":"Haas B, Grenier D (2018) Understanding the virulence of Streptococcus suis: a veterinary, medical, and economic challenge. 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