Map, but not EspF, induces breast epithelial cell apoptosis through ERK/DRP-1 pathway

• Published in: Veterinary microbiology 2022-03, Vol.266, p.109367-109367, Article 109367
• Main Authors: Li, Yanan, Zhu, Yaohong, Chu, Bingxin, Liu, Ning, Chen, Shiyan, Wang, Jiufeng
• Format: Article
• Language: English
• Subjects: Apoptosis; Bovine mastitis; Breast; E. coli; Epithelial cells; ERK; Escherichia coli; EspF; Extracellular signal-regulated kinase; Lymphocytes T; Mastitis; Membrane potential; Mitochondria; Signal transduction; Tight junctions; Virulence factors
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2022.109367

Map, not EspF, is vital virulence factor of E. coli-induced apoptosis though ERK/DRP-1 signaling pathway.E. coli (EPEC) secretes effector protein-Map and -EspF through the type III secretion system. Map, not EspF, to activate the ERK signaling pathway, which decreases the levels of MFN-1, MFN-2 and p-DRP-1 (ser637) and increases the level of DRP-1. Map and EspF promotes mitochondrial fission (mitochondrial fragmentation), the continuous opening of mPTP and a decrease in MMP. Then it causes the release of pro-apoptotic factor Cyt-C and Ca2+, and increased the caspase 3 activation. Eventually this causes cell apoptosis. The black arrows indicate promotion. The red arrow represents the level increase or decrease. Red X represents no. [Display omitted] •Map and EspF could destroy tight junction.•Map and EspF are vital effectors in E. coli-induce apoptosis in bovine mastitis.•Map, not EspF, could activate ERK signaling pathway The incidence of bovine mastitis induced by enteropathogenic Escherichia coli (EPEC) in the environment has increased, but the mechanism of effector-Map and -EspF secreted by EPEC in breast epithelial cells is not clear. Therefore, this study focused on Map and EspF to explore the role of these two virulence factors in EPEC-induced bovine mastitis. We established Δmap and/or ΔEspF mutant strains to explore their role in EPEC-induced bovine mastitis. It was found that both Map and EspF could affect the mitochondrial membrane potential, apoptosis, and tight junctions in MAC-T cells. In addition, we also found that Map could affect the ERK signaling pathway. In order to further verify the effect of Map on the ERK signaling pathway, we introduced an ERK inhibitor (PD98059) and pc DNA3.1 plasmid with the map gene. It was found that DRP-1 and apoptosis were no longer affected by Map. In summary, the study implies that E. coli can promote breast epithelial cell apoptosis and destroy tight junctions through Map and EspF. However, Map, but not EspF, induces breast epithelial cell apoptosis through the ERK-DRP-1 pathway.