Enteropathogenic Escherichia coli (EPEC) is a gastrointestinal pathogen that utilises a type III secretion system (T3SS) to inject virulence effector proteins directly into intestinal cells in order to subvert host cell signaling pathways.  Among these effectors is NleB1 which binds to the Fas associated death domain (FADD) protein during infection.

 FADD is an adaptor protein possessing a death domain (DD) that mediates extrinsic host signaling from the death receptors Fas and TNFR.  Stimulation of Fas by its ligand, FasL, induces recruitment of FADD and subsequently caspase-8, followed by auto-proteolytic cleavage of caspase-8 and apoptotic cell death.  Consistent with its ability to bind FADD, NleB1 prevents FasL and TNF induced caspase-8 cleavage and blocks FasL-induced cell death.

 Strong homologues of NleB1 are found in Salmonella Typhimurium and these are termed SseK1, SseK2 and SseK3.  We hypothesized that the SseK effectors would also bind to DD proteins and inhibit apoptotic or inflammatory signaling. Detection of caspase-8 cleavage during S. Typhimurium infection showed that none of the SseK effectors played a strong role in the inhibition of caspase-8 cleavage. This is consistent with the fact that we could not detect binding of the SseKs to Fas or FADD. In fact S. Typhimurium appeared to stimulate caspase-8 cleavage in a T3SS (SPI-1) dependent manner. A further survey of DD proteins revealed that SseK3 bound to TNFR1 however S. Typhimurium did not appear to inhibit TNF-induced IL-8 production. We conclude that the SseKs have an alternative function during S. Typhimurium infection to NleB1 in EPEC.