Expression of microbial virulence proteins in Saccharomyces cerevisiae models mammalian infection

Bacterial virulence proteins that are translocated into eukaryotic cells we re expressed in Saccharomyces cerevisiae to model human infection. The subc ellular Localization patterns of these proteins in yeast paralleled those p reviously observed during mammalian infection, including localization to th e nucleus and plasma membrane, Localization of Salmonella SspA in yeast pro vided the first evidence that SspA interacts with actin in living cells. In many cases, expression of the bacterial virulence proteins conferred genet ically exploitable growth phenotypes. In this way, Yersinia YopE toxicity w as demonstrated to be linked to its Rho GTPase activating protein activity. YopE blocked polarization of the yeast cytoskeleton and cell cycle progres sion, while SspA altered polarity and inhibited depolymerization of the act in cytoskeleton, These activities are consistent with previously proposed o r demonstrated effects on higher eukaryotes and provide new insights into t he roles of these proteins in pathogenesis: SspA in directing formation of membrane ruffles and YopE in arresting cell division. Thus, study of bacter ial virulence proteins in yeast is a powerful system to determine functions of these proteins, probe eukaryotic cellular processes and model mammalian infection.