bacterial effector protein NleA, and similar proteins
This family includes non-locus of enterocyte effacement (non-LEE) encoded effector A (NleA), a bacterial effector protein injected by enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC), both related strains capable of inducing severe gastrointestinal disease. These pathogens modulate cellular functions via the deployment of effector proteins in a type three secretion system (T3SS)-dependent manner. In response, the host Nod-like receptor pyrin domain containing (NLRP) inflammasome activates caspase-1 and releases IL-1beta. NleA plays a role in controlling the host immune response through targeting of Nod-like receptor 3 (NLRP3); it has been identified as the effector that can subdue IL-1beta secretion by inhibiting caspase-1 activation, thus inhibiting NLRP inflammasome activation. NleA interacts with NLRP3 via regions containing the PYD and LRR domains. NleA has also been shown to associate with non-ubiquitinated and ubiquitinated NLRP3 and to interrupt de-ubiquitination of NLRP3, which is a required process for inflammasome activation.