Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3

Salmonella Stealth Bomber Salmonella secretes a virulence factor, SipA, which helps it to invade epithelial cells of the gut. During invasion, the host cell is triggered into synthesizing and secreting the apoptotic enzyme caspase-3. Srikanth et al. (p. 390 ) now show that instead of being extinguished as the host cell collapses into programmed cell death, during the early stages of infection, Salmonella diverts the host enzyme to its own use. The SipA protein has amino acid motifs that are recognized by caspase-3, which cleaves the bacterial protein into active virulence effectors: one stimulates actin polymerization to help cell entry and the other induces inflammation. If the caspase motif contains a single-point mutation, then virulence is lost in mouse models of infection. Conversely, caspase-deficient mice suffer less from Salmonella -induced gastroenteritis.