Vav2 is a master regulator of repair against bacterial pore-forming toxins.

ABSTRACT: Necrotizing soft tissue infections (NSTIs) kill 25-35% of patients despite antibiotic treatment. Two causes of NSTIs are Streptococcus pyogenes and Clostridium perfringens. They produce the cholesterol-dependent cytolysins (CDCs) streptolysin O (SLO) and perfringolysin O (PFO). CDCs damage cell membranes. Cells resist this damage using Ca²⁺-dependent repair pathways, including MEK-dependent microvesicle shedding, dysferlin-mediated patch repair, and annexin-mediated membrane clogging. While 70% of this repair is MEK-dependent, the upstream regulators are unclear. Here, we show that the Rac GEF Vav2, triggers MLK3-MEK-dependent repair. Inhibiting or knocking down Vav2 sensitized multiple cell types to CDCs, whereas blocking other Rac GEFs did not. Vav2 accounted for

SUBMITTER: Kayejo VG 

PROVIDER: S-EPMC12324502 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature