Enteropathogenic E. coli infection co-elicits lysosomal exocytosis and lytic host cell death

Enteropathogenic Escherichia coli (EPEC) is a primary human enteric bacterial pathogen causing acute diarrhea in children. EPEC colonizes the small intestine, and the disease is induced, in part, by the ability of the pathogen to utilize a type III secretion machinery to inject a battery of proteins, termed effectors, from the bacterial cytoplasm into the intestinal enterocytes. Host cell responses to the infecting pathogen are also essential for disease development. Despite intensive research, the mechanisms of EPEC infection and host cell responses need to be better understood. Here, we show that specific EPEC type III secreted effectors, EspF and Map, induce lytic host cell death and also lysosomal exocytosis (LE), resulting in the secretion of lysosomal enzymes into the extracellular environment and the appearance of the lysosomal membrane proteins, Lamp-1, on the infected cell surface. The mitochondrial cytotoxicity and the guanine nucleotide exchange factor domains of Map have been identified to be involved in these processes. In contrast, EspZ, an EPEC effector that protects against lytic cell death, also inhibits LE. Our results combined suggest that LE and host cell death are tightly interconnected processes. The mechanisms and functional significance of these processes on EPEC infection are discussed.

Automated summary

This study found that specific EPEC type III secreted effectors, EspF and Map, can induce lytic host cell death and lysosomal exocytosis (LE), resulting in the secretion of lysosomal enzymes into the extracellular environment and the appearance of the lysosomal membrane protein, Lamp-1, on the infected cell surface. Meanwhile, an EPEC effector, EspZ, inhibits LE and protects against lytic cell death.