Genome-wide Characteristics, Antibiotic Resistance, and Pathogenicity Analysis of Streptococcus parasuis Strains Isolated from Diseased Pigs

Abstract Streptococcus parasuis is currently not only an underestimated zoonotic pathogen but also a bacterial source of infection in food animals, posing a potential threat to global public health. Despite increased reports in recent years, systematic studies in Northwest China remain scarce. However, the lack of complete genomic sequence information has limited in-depth bioinformatics analysis of multidrug-resistant Streptococcus parasuis isolated from pigs. This study reports the whole-genome sequencing results of Streptococcus parasuis strain A1 isolated from pigs. The A1 genome consists of a single circular chromosome without circular plasmids, establishing it as a potential “blank” vector for constructing standardized gene cloning and expression systems in genetic engineering. Twenty-one antibiotic resistance genes were identified on the bacterial chromosome, conferring resistance to major antibiotics including glycopeptides, macrolides, lincosamides, streptogramins, aminoglycosides, tetracyclines, fluoroquinolones, cephalosporins, polypeptides, and β-lactams. Resistance mechanisms encompass target site modification, target site protection, antibiotic inactivation, and efflux pump-mediated drug efflux, demonstrating potent multidrug resistance potential. Additionally, 113 virulence factors were identified, spanning multiple functional domains including effector protein secretion systems, immune regulation, adhesion, stress survival, and biofilm formation. Among these, six virulence factors relate to nutritional metabolism, primarily involving iron uptake, pyrimidine biosynthesis, purine biosynthesis, and fatty acid metabolism. Antibiotic susceptibility testing confirmed the multidrug-resistant phenotype of this strain. Mouse infection experiments demonstrated that strain A1 exhibits strong pathogenicity, causing lethal infections in mice and significant histopathological damage to organs such as the liver and spleen. Concurrently, levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) were significantly elevated in the serum of infected mice. Whole-genome analysis revealed 24 horizontal gene transfer elements in A1, including 3 genomic islands, 13 transposons, and 8 remnant pre-phage sequences. Furthermore, 196 virulence-attenuating mutations and 10 potential pathogenicity-related deletion sites were identified. Further analysis on the A1 chromosome identified 4 core antibiotic target genes and 10 lethal mutation sites, which may serve as potential new targets for preventing, controlling, and treating infections caused by this bacterium. Therefore, this study contributes to the development of strategies for preventing and controlling Streptococcus suis infections and their spread within pig populations. It should be emphasized that this study is based solely on analysis of a single strain, and the generalizability of its conclusions requires validation with additional strains. Furthermore, the correspondence between resistance genes and phenotypes, as well as the specific regulatory and synergistic mechanisms of virulence factors, remain incompletely elucidated and warrant further investigation.