A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion

An essential feature of the bacterial pathogen Salmonella spp. is its abili ty to enter cells that are normally non-phagocytic, such as those of the in testinal epithelium(1). The bacterium achieves entry by delivering effector proteins into the host-cell cytosol by means of a specialized protein-secr etion system (termed type III), which causes reorganization of the cell's a ctin cytoskeleton and ruffling of its membrane(2-4). One of the bacterial e ffecters that stimulates these cellular responses is SopE, which acts as a guanyl-nucleotide-exchange factor on Rho GTPase proteins such as Cdc42 and Rac (ref. 5). As the actin-cytoskeleton reorganization induced by Salmonell a is reversible and short-lived, infected cells regain their normal archite cture after bacterial internalization(6,7). We show here that the S. Typhim urium effector protein SptP, which is delivered to the host-cell cytosol by the type-III secretion system, is directly responsible for the reversal of the actin cytoskeletal changes induced by the bacterium. SptP exerts this function by acting as a GTPase-activating protein (GAP) for Rac-1 and Cdc42 .