RhoB promotesSalmonellasurvival by regulating autophagy

Abstract

AbstractSalmonella entericaserovar Typhimurium manipulates cellular Rho GTPases for host cell invasion by effector protein translocation via the Type III Secretion System (T3SS). The two Guanine nucleotide exchange (GEF) mimicking factors SopE and –E2 and the inositol phosphate phosphatase (PiPase) SopB activate the Rho GTPases Rac1, Cdc42 and RhoA, thereby mediating bacterial invasion.S.Typhimurium lacking these three effector proteins are largely invasion-defective. Type III secretion is crucial for both early and later phases of the intracellular life ofS.Typhimurium. Here we investigated whether and how the small GTPase RhoB, known to localize on endomembrane vesicles and at the invasion site ofS.Typhimurium, contributes to bacterial invasion and to subsequent steps relevant forS.Typhimurium lifestyle.We show that RhoB is significantly upregulated within hours ofSalmonellainfection. This effect depends on the presence of the bacterial effector SopB, but does not require its phosphatase activity. Our data reveal that SopB and RhoB bind to each other, and that RhoB localizes on early phagosomes of intracellularS.Typhimurium. Whereas both SopB and RhoB promote intracellular survival ofSalmonella, RhoB is specifically required forSalmonella-induced upregulation of autophagy. Finally, in the absence of RhoB, vacuolar escape and cytosolic hyper-replication ofS.Typhimurium is diminished. Our findings thus uncover a role for RhoB inSalmonella-induced autophagy, which supports intracellular survival of the bacterium and is promoted through a positive feedback loop by theSalmonellaeffector SopB.