Enterobacterial factors antagonize host defense

This Reactome event describes mechanisms used by intracellular bacterial pathogens that deploy type III secretion system (T3SS) effectors to inhibit caspase-4 (CASP4)-mediated pyroptosis, a lytic form of cell death triggered during infection. Specifically, Shigella flexneri secretes OspC3, which catalyzes ADP-riboxanation of CASP4, thereby inhibiting its catalytic activity and blocking lipopolysaccharide (LPS)-induced pyroptosis (Kobayashi T et al., 2013; Li Z et al., 2021; Hou Y et al., 2023). Pathogenic Escherichia coli strains secrete the T3SS effector NleF, which directly binds and inhibits CASP4 as well as apoptotic caspases CASP8 and CASP9 (Blasche S et al., 2013). The crystal structure of the NleF:CASP9 complex revealed a novel inhibitory mechanism involving insertion of the NleF carboxy-terminus into the protease active site (Blasche S et al., 2013). Bacterial NleF blocks CASP4 activation in vitro and also inhibits CASP4 during enteropathogenic (EPEC) or enterohemorrhagic (EHEC) infection in epithelial cells (Pallett MA et al., 2017; Song T et al., 2017). During EPEC infection, NleF suppresses CASP4 activity and CASP4-dependent interleukin-18 (IL-18) processing (Pallett MA et al., 2017).

Summary from Reactome (R-HSA-9956593), read 2026-09-23.