PNNL

Abstract

Many pathogenic bacteria of the family Enterobacteriaceae have Type 3 Secretion Systems that inject virulence factors named effectors into the host cell cytosol. Although several effectors have been shown to help bacteria to invade and survive inside host cells, the function and host targeted pathways of most of the effectors identified to date is largely unknown. To gain more knowledge on host proteins targeted by bacterial effectors we performed co-affinity purification of host proteins from cell lysates using recombinant effectors from the Enterobacteriaceae intracellular pathogens, Salmonella enterica serovar Typhimurium and Citrobacter rodentium. We identified 58 host interactors for the Salmonella effectors GogA, GtgA, GtgE, SpvC, SrfH, SseL, SspH1 and SssB and 33 interactors for the Citrobacter effectors EspT, NleA, NleC, NleE, NleG1 and NleK. We biochemically validated the interaction between the Salmonella protein SrfH and the host protein kinase ERK2, which revealed a role of this effector in regulating the phosphorylation levels of this enzyme that plays a central role in signal transduction.