Deletion of the sodA Gene Impaired the Pathogenicity of Streptococcus suis Serotype 2 to Mice by Inhibiting Caspase-1/GSDMD Pathway Activation in Macrophages.

Streptococcus suis serotype 2 (SS2) is a major zoonotic pathogen causing infectious disease in various species, whose pathogenesis is still not well understood. The sodA gene is an important virulence gene of SS2 involved in the host's immune response against pathogens. This study aimed to explore the impact of superoxide dismutase A (sodA) gene deletion on the pathogenicity of SS2 to mice. In this study, mice were grouped as control, WT, and ΔsodA, which were intraperitoneally injected with PBS, wild-type strain HA9801, and ΔsodA strain, respectively. WT proved to be a more virulent strain to mice with higher bacterial loads and survival rates in mice than those for ΔsodA. Moreover, more-severe tissue damage was observed in the lungs, liver, spleen, and kidneys of mice injected with WT than with ΔsodA. Additionally, macrophages accumulate to defend against SS2, and the results indicated that sodA gene deficiency decreased macrophage recruitment. In in vitro studies, caspase-1 and gasdermin D (GSDMD) were activated in macrophages induced by SS2; however, the absence of the sodA gene significantly inhibited the expression of pro-caspase-1, caspase-1, and GSDMD-N. Moreover, deletion of the sodA gene also decreased Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) release in macrophages induced by SS2. Taken together, the absence of the sodA gene alleviated the pathogenicity of SS2 as a result of decreased macrophage accumulation and breakage of the caspase-1/GSDMD pathway in macrophages.