SodA promotes immune evasion of Streptococcus suis by suppressing ROS accumulation and GSDMD-mediated mitochondrial...

Streptococcus suis is a major swine pathogen that poses a serious threat to pig health. Resistance to oxidative stress and modulation of host immune responses are both critical for the survival of S. suis serotype 2 (SS2) strains during infection. In this study, we investigated the role of the sodA gene in SS2 survival, neutrophil responses, and mitochondrial function, focusing particularly on neutrophil extracellular trap (NET) formation. Using a murine peritoneal infection model, we found that sodA deletion significantly reduced neutrophil recruitment. In vitro assays with primary mouse neutrophils further demonstrated that the sodA mutant exhibited reduced intracellular survival and elevated levels of reactive oxygen species (ROS) in neutrophils. The mutant also triggered more robust NET formation, as indicated by significantly increased levels of cell-free DNA and MPO-DNA complexes. Importantly, the inclusion of a complemented strain confirmed restoration of ROS clearance and normalization of NETs-associated markers, supporting the specificity of the sodA-dependent phenotype. Moreover, sodA deficiency exacerbated SS2-induced mitochondrial membrane depolarization and ROS accumulation in neutrophils. Notably, it also enhanced the expression of cleaved gasdermin D (GSDMD-N), which colocalized with mitochondria and likely contributed to mitochondrial damage and NET induction. Collectively, these findings suggest that sodA facilitates SS2 immune evasion by suppressing host ROS accumulation and GSDMD-N-mediated mitochondrial disruption, thereby limiting NET formation and promoting bacterial survival.

Streptococcus suis is a major swine pathogen with significant economic and zoonotic implications. Neutrophil extracellular traps (NETs) are essential for host defense, but their regulation by bacterial factors remains poorly understood. This study identifies the superoxide dismutase gene sodA as a key factor in immune evasion by S. suis. We demonstrate that sodA deletion enhances reactive oxygen species accumulation, mitochondrial damage, and NETs formation in neutrophils, impairing bacterial survival. These findings reveal a novel mechanism by which S. suis modulates host innate immunity and highlight sodA as a potential target for enhancing host defense against S. suis serotype 2 infection.