Beth McCormick’s laboratory has discovered a novel strategy Salmonella uses to subvert host defense

Beth McCormick - News Article Pic

The McCormick laboratory has discovered that the bacterium often responsible for food poisoning, Salmonella enterica Typhimurium, exploits an enzyme produced by the host's intestinal cells to help this pathogen to invade them. During invasion, the host cell is tricked into synthesizing and secreting the apoptotic enzyme caspase-3. But 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 Salmonella virulence protein, SipA, 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-3 deficient mice suffer less from Salmonella-induced gastroenteritis. Also, this strategy isn’t limited to SipA. Other proteins that are injected by Salmonella, and those from other gut bacteria like Escherichia coli and Shigella flexneri, also carry targets for caspase-3. And the majority of these proteins, like SipA, have two functions, with different ends performing different jobs. Thus, it appears that many enteric pathogens have managed to subvert these defenses, using the executioner protein to activate and double their own arsenal. Srikanth CV, Wall DM, Maldonado-Contreras A, Shi HN, Zhou D, Demma Z, Mumy KL, McCormick BA. Science. 2010 Oct 15;330(6002):390-3. (Pictured L-R: C.V. Srikanth, Beth McCormick, Ana Maldonado-Contreras)