A LXG toxin stabilized by DUF4176 contributes to Streptococcus suis competition and pathogenicity.

Background: Streptococcus suis poses a significant threat to both humans and pigs, causing severe disease such as meningitis, septicaemia, and sudden death. The type VII secretion system (T7SS) plays a crucial role in exporting effectors that mediate bacterial competition and colonization in polymicrobial environments. Although Leu-x-Gly (LXG) polymorphic toxins are among the main effectors secreted by the T7SS, the mechanism underlying their secretion remains to be fully elucidated.

Results: Here, we identified a complex repertoire of LXG effectors in S. suis, comprising at least five distinct LXG-domain groups and 14 C-terminal toxin types. We focused on one LXG effector, LXG1-CT3, from the virulent strain WUSS351, demonstrating its pore-forming activity and essential role in S. suis competition and virulence. Additionally, we discovered that a small protein family, DUF4176, partners with each cognate C-terminal toxin, stabilizing the corresponding LXG effector prior to secretion, thereby enhancing bacterial competitiveness.

Conclusions: These findings deepen our understanding of S. suis competition and pathogenesis, while offering new insights into the T7SS-mediated secretion of LXG effectors.