Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Int J Mol Sci. 2022 Apr 28;23(9):4907. doi: 10.3390/ijms23094907.
Bovine mastitis seriously affects bovine health and dairy product quality. is the most important pathogen in the environment and dairy products. Enteropathogenic (EPEC) is a zoonotic pathogen, which seriously threatens the health of people and dairy cows. We recently reported that 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 mutant, complementary strain, and recombinant plasmid Map. 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 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.
牛乳腺炎严重影响牛的健康和乳制品质量。 是环境和乳制品中最重要的病原体。肠致病性大肠杆菌（EPEC）是一种人畜共患病病原体，严重威胁着人和奶牛的健康。我们最近报道， 可以诱导牛乳腺上皮细胞内源性细胞凋亡。然而，EPEC 破坏线粒体和诱导牛乳腺炎的机制尚不清楚。在本研究中，我们发现 EPEC 可以诱导依赖 DRP-1 的线粒体裂变和凋亡。这一点通过应用 DRP-1 抑制剂 Mdivi 得到了验证。同时，为了验证 Map 毒力因子在 EPEC 诱导的牛乳腺炎中的作用，我们构建了 缺失突变体、互补菌株和重组质粒 Map。在本研究中，我们发现 Map 诱导了 DRP-1 介导的线粒体裂变，导致线粒体功能障碍和细胞凋亡。这些推论在体内通过建立小鼠乳腺炎模型得到了进一步验证。敲除 基因后，小鼠的乳腺炎症和细胞凋亡明显减轻。所有结果表明，EPEC 通过分泌 Map 毒力因子靶向线粒体，诱导 DRP-1 介导的线粒体裂变、线粒体功能障碍和牛乳腺炎中的内源性细胞凋亡。
