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

Abstract

An essential feature of the bacterial pathogen Salmonella spp. is its ability to enter cells that are normally non-phagocytic, such as those of the intestinal epithelium¹. The bacterium achieves entry by delivering effector proteins into the host-cell cytosol by means of a specialized protein-secretion system (termed type III), which causes reorganization of the cell's actin cytoskeleton and ruffling of its membrane^2,3,4. One of the bacterial effectors 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 Salmonella is reversible and short-lived, infected cells regain their normal architecture after bacterial internalization^6,7. We show here that the S. Typhimurium 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.