Mechanisms Underlying the Effects of Secretory Protein G22 on Biological Characteristics and Virulence of Streptococcus suis

<i>Streptococcus suis</i> serotype 2 (SS2) is an important zoonotic pathogen that seriously harms the swine industry and human health. However, its pathogenic mechanisms are largely unknown, and the few virulence factors reported so far are insufficient to systematically explain its infectious and pathogenic mechanisms. In preliminary research, we identified a gene named <i>G22</i> encoding a hypothetical secreted protein that may be closely associated with the high-level pathogenicity of <i>S. suis</i>. In this study, we constructed deletion and complementation strains of the <i>G22</i> gene through homologous recombination and explored its roles in the pathogenicity and susceptibility of <i>S. suis</i> to environmental stresses through in vitro and in vivo experiments. The deletion of <i>G22</i> clearly influenced the typical capsular structure of SS2 and impaired the bacterium's growth in a medium containing hydrogen peroxide (showing a growth reduction of 32.98% ± 5.23% compared to the wild-type strain SC19, <i>p</i> < 0.001) or with a low pH (with a growth inhibition of 17.44% ± 1.9% relative to the wild-type strain SC19, <i>p</i> < 0.01). Δ<i>G22</i> also showed reduced survival in whole blood and in RAW 264.7 macrophages (with a survival reduction of 16.44% ± 2.29% compared to the wild-type, <i>p</i> < 0.001). The deletion of <i>G22</i> also sharply attenuated the virulence of SS2 in a mouse infection model (reducing the mortality rate by 50% ± 0.04%, <i>p</i> < 0.05). We also demonstrated that <i>G22</i> is required for the adhesion and invasion of SS2 in host cells. An RNA sequencing analysis revealed that 50 genes were differentially expressed in the Δ<i>G22</i> and wild-type strains: 23 upregulated and 37 downregulated. Many of the genes are involved in carbohydrate metabolism and the synthesis of virulence-associated factors. Several genes associated with the phosphotransferase system were significantly upregulated in strain Δ<i>G22</i>. In summary, <i>G22</i> plays a role in the morphological development and pathogenesis of the highly virulent SS2 strain SC19.