A toxic effector of T7SS facilitates bacterial competition and virulence through membrane damage in Streptococcus...

Streptococcus suis is a zoonotic pathogen that poses a significant threat to both the swine industry and human health. This bacterium utilizes a type VII secretion system (T7SS) to translocate effector proteins that mediate bacterial competition and contribute to virulence. However, the functions of T7SS effectors in S. suis remain poorly understood. In this study, we identified and characterized LXG-T2, a T7SS-secreted toxin from S. suis virulent strain WUSS351. Bioinformatics analysis revealed that LXG-T2 harbors a C-terminal glycine zipper motif, a structural feature commonly associated with membrane-disrupting toxins. Functional assays demonstrated that LXG-T2 exhibits strong bactericidal activity against E. coli and provides S. suis with a competitive advantage. Furthermore, the LXG-T2 has the capacity to compromise the integrity of bacterial membranes, as evidenced by the observed increase in membrane permeability and depolarization in target cells. Moreover, LXG-T2 exhibited cytotoxic effects on host cells and promoted S. suis survival in a murine infection model. Collectively, our findings establish LXG-T2 as a T7SS effector mediated membrane disruption to enhance both bacterial competition and virulence. This work not only reveals a novel mechanism by which S. suis manipulates microbial communities, but also highlights the significance of T7SS effectors as key mediators of pathogenesis in Gram-positive bacteria.