Population Genetic Architecture of the Streptococcus suis Antigen HP0197

S. suis is a major zoonotic infectious disease whose serological diversity brings challenges to vaccine development. Based on the whole-genome data of 169 S. suis strains, this study conducted a systematic bioinformatics analysis of the surface antigen protein HP0197 that reveals its distribution characteristics, sequence diversity, domain composition and antigenic epitope distribution. The results showed that the HP0197 gene, which has a detection rate of 91.72%, can be divided into seven major phylogroups (I–VII) and the following two structural types: short form (HP0197-S) and long form (HP0197-L). All sequences contained signal peptides, transmembrane structures, LPXTG anchoring motifs, as well as conserved GAGBD and G5 domains, among which tandem repeats of the G5 domain existed in the long HP0197-L type. Tertiary structure prediction indicated that HP0197 has a spatial architecture of “conserved at both ends and flexible in the middle”, in which B-cell epitopes are mainly enriched near the GAGBD and G5 domains, suggesting these regions are the key targets for inducing cross-immune protection. It systematically elucidates the diversity and structural characteristics of the HP0197 protein from the perspective of population genetics, which provides a theoretical basis for optimizing existing subunit vaccines, designing broad-spectrum multi-epitope vaccines and exploring novel anti-infection strategies.