Bacterial pathogenesis: Pathogenic bacteria attack RHIM

Abstract

Attaching and effacing enteropathogenic Escherichia coli causes gastrointestinal inflammation and diarrhoea. In this issue of Nature Microbiology, Pearson and colleagues find that this pathology involves bacterial cleavage of a class of host cell death signal adaptors that encode a unique protein interaction motif called the RHIM.

Figure 1

RHIM protein cleavage in EPEC infection. a, In uninfected enterocytes, RHIM domain (green boxes)-containing proteins can promote inflammatory cytokine production and necroptosis. RIPK1 and RIPK3 assemble into a higher-order complex when activated. b, EPEC injects the cysteine protease EspL effector upon host cell infection, which leads to cleavage of RHIM domain-containing proteins. RIPK1 and RIPK3 degradation is thought to prevent their assembly and thus block necroptosis, while TRIF and DAI cleavage may also downregulate IFN signalling. EspL is required to combat host clearance as infection with an inactive EspL strain reduces C. rodentium intestinal persistence.