文献类型：期刊文献

英文题名：Edwardsiella piscicida Enters Nonphagocytic Cells via a Macropinocytosis-Involved Hybrid Mechanism

作者：Hu, Tianjian[1];Zhang, Lingzhi[1,4,5];Wang, Wei[1];Yang, Dahai[1,2];Xiao, Jingfan[1,2];Zhang, Yuanxing[1,2,3];Liu, Xiaohong[1,2];Liu, Qin[1,2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Shanghai Engn Res Ctr Maricultured Anim Vaccines, Shanghai, Peoples R China;[3]Shanghai Collaborat Innovat Ctr Biomfg Technol, Shanghai, Peoples R China;[4]Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA;[5]Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA

年份：2019

卷号：201

期号：5

外文期刊名：JOURNAL OF BACTERIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000459546800002)】；

基金：This study was supported by the NSFC grants 31672696 to J.X., 31472308 to Q.L., and 31622059 to Q.L.

语种：英文

外文关键词：Edwardsiella piscicida; endocytosis; internalization; macropinocytosis; nonphagocytic cells

摘要：Edwardsiella piscicida is an important pathogen that infects a wide range of hosts from fish to human. Recent studies demonstrated that E. piscicida can invade and survive within multiple nonphagocytic cells, but the internalization mechanism remains poorly understood. Here, we used HeLa cells as a nonphagocytic cell model to investigate the endocytic strategy used by the pathogenic E. piscicida isolate EIB202. Using a combination of optical and electron microscopy, we observed obvious membrane ruffles and F-actin rearrangements in HeLa cells after EIB202 infection. We also revealed that EIB202 internalization significantly depended on the activity of Na+/H+ exchangers and multiple intracellular signaling events related to macropinocytosis, suggesting that E. piscicida utilizes the host macropinocytosis pathway to enter HeLa cells. Further, using inhibitory drugs and shRNAs to block specific endocytic pathways, we found that a caveolin-dependent but not clathrin-dependent pathway is involved in E. piscicida entry and that its entry requires dynamin and membrane cholesterol. Together, these data suggest that E. piscicida enters nonphagocytic cells via macropinocytosis and caveolindependent endocytosis involving cholesterol and dynamin, improving the understanding of how E. piscicida interacts with nonphagocytic cells. IMPORTANCE Bacterial internalization is the first step in breaking through the host cell defense. Therefore, studying the mechanism of bacterial internalization improves the understanding of the pathogenic mechanism of bacteria. In this study, the internalization process on nonphagocytic cells by Edwardsiella piscicida was evaluated. Our results showed that E. piscicida can be internalized into nonphagocytic cells via macropinocytosis and caveolin-mediated endocytosis, and that cholesterol and dynamin are involved in this process. These results reveal a new method for inhibiting E. piscicida infection, providing a foundation for further studies of bacterial pathogenicity.