Disruption of fas-fas ligand signaling, apoptosis, and innate immunity by bacterial pathogens

Yersinia pestis, the causative agent of the disease plague, prevents Fas induction by cleaving and inactivating FasL on the surface of effector cells, while enteropathogenic Escherichia coli (EPEC), a cause of gastrointestinal infections, post-translationally modifies FADD within target cells to arrest Fas-induced apoptosis (Figure 1).\n Two independent groups showed that the EPEC T3SS effector NleB disrupts FADD-mediated apoptosis downstream of Fas-FasL engagement within target cells to counteract host defenses and enhance colonization [37], [38]. Despite our limited mechanistic understanding of cell death manipulation by pathogens, therapeutics that prevent bacterial virulence factors from modulating apoptotic cell death may have broad implications. Since both Pla of Y. pestis and NleB of EPEC disable Fas-FasL signaling to promote virulence, the administration of proapoptotic compounds, exogenous FasL protein, or agonistic antibodies that trimerize Fas may serve as possible therapeutics [39].