Phosphoproteomic analysis of Salmonella-infected cells identifies key kinase regulators and SopB-dependent host...

Salmonella enterica is a bacterial pathogen that causes gastroenteritis and typhoid fever. Virulence is achieved by two type III secretion systems that translocate effector proteins into host cells, where they mimic or block host protein function. Effectors translocated into host cells by the first type III secretion system facilitate invasion and stimulate intracellular signaling cascades leading to inflammation. Here, we performed global temporal analysis of host signaling events induced during the initial stages of Salmonella infection and identified the dynamics of host protein phosphorylation as well as differences between growth factor-stimulated and bacteria-induced signaling. Informatics analysis predicted that sites with altered phosphorylation in infected cells were targeted by the serine-threonine kinases Akt, protein kinase C, and Pim and that up to half of the host phosphorylation events detected after Salmonella infection required the effector protein SopB. Our data reveal extensive manipulation of host phosphorylation cascades by this Salmonella effector and provide a detailed map of the events leading to intestinal inflammation, which is the crucial host response that enables Salmonella to proliferate in the intestine.