A surface protein identified from Streptococcus suis serotype 2 exhibits neutrophil-resistant ability via its polysaccharide capsule.

Streptococcus suis serotype 2 (SS2) is an emerging zoonotic agent responsible for a variety of diseases. The septicemia caused by SS2 suggests that it can evade the bactericidal effects of innate immune cells. However, the mechanisms by which SS2 evades innate immunity remain largely unknown. Neutrophils are critical components of innate immunity for antimicrobial defense. In this study, we identified a cell surface protein (CSP) insertion mutant in an SS2 transposon mutant library that significantly induces neutrophil extracellular traps (NETs) and shows poor survival compared to the parent SS2 in the bloodstream. CSP deletion mutant (ΔCSP) was constructed and it exhibits a defective polysaccharide capsule and enhanced biofilm formation. Although ΔCSP induces increased NET release and ROS formation, its survival and proliferation within neutrophils and NETs are significantly reduced. Additionally, ΔCSP stimulates extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in neutrophils, which may enhance neutrophil bactericidal activity. Importantly, purified polysaccharide capsule from SS2 can inhibit neutrophil bactericidal effects. This study identifies bacterial virulence factors that prevent SS2 clearance by neutrophils, offering potential antigens or drug targets for the prevention and control of swine streptococcosis.