Map of Enteropathogenic Escherichia coli Targets Mitochondria and Triggers DRP-1-Mediated Mitochondrial Fission and Cell Apoptosis in Bovine Mastitis

Abstract

Bovine mastitis seriously affects bovine health and dairy product quality. <i>Escherichia coli</i> is the most important pathogen in the environment and dairy products. Enteropathogenic <i>Escherichia coli</i> (EPEC) is a zoonotic pathogen, which seriously threatens the health of people and dairy cows. We recently reported that <i>E. coli</i> can induce endogenous apoptosis in bovine mammary epithelial cells. However, the mechanism of EPEC-damaged mitochondria and -induced bovine mastitis is unclear. In this study, we found that EPEC can induce DRP-1-dependent mitochondrial fission and apoptosis. This was verified by the application of Mdivi, a DRP-1 inhibitor. Meanwhile, in order to verify the role of the Map virulence factor in EPEC-induced bovine mastitis, we constructed a <i>map</i> mutant, complementary strain, and recombinant plasmid Map_His. In the present study, we find that Map induced DRP-1-mediated mitochondrial fission, resulting in mitochondrial dysfunction and apoptosis. These inferences were further verified in vivo by establishing a mouse mastitis model. After the <i>map</i> gene was knocked out, breast inflammation and apoptosis in mice were significantly alleviated. All results show that EPEC targets mitochondria by secreting the Map virulence factor to induce DRP-1-mediated mitochondrial fission, mitochondrial dysfunction, and endogenous apoptosis in bovine mastitis.