期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 291, 期 52, 页码 26837-26849出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.757393
关键词
-
资金
- NIDDK
- National Institutes of Health [1R01DK105118-01]
- Swim Across America Cancer Research Award
- University of Illinois at Chicago Cancer Center
- Projects of International Cooperation and Exchanges National Natural Science Foundation of China [31320103907]
- Graduate Research and Innovation Project of Jiangsu Province [KYZZ_0368]
- International Program for Ph.D. students from Yangzhou University
Salmonella pathogenesis studies to date have focused on Salmonella typhimurium, and the pathogenesis of a second major serotype, Salmonella enteritidis, is poorly understood. Salmonella spp. possess effector proteins that display biochemical activities and modulate host functions. Here, we generated a deletion mutant of the effector AvrA, S.E-AvrA(-), and a plasmid-mediated complementary strain, S.E-AvrA(-)/pAvrA(+) (S.E-AvrA(+)), in S. Enteritidis. Using in vitro and in vivo infection models, we showed that AvrA stabilizes epithelial tight junction (TJ) proteins, such as ZO-1, in human intestinal epithelial cells. Transepithelial electrical resistance was significantly higher in cells infected with S.E-AvrA(+) than in cells infected with S.E-AvrA(-). Inhibition of the JNK pathway suppresses the disassembly of TJ proteins; we found that enteritidis AvrA inhibited JNK activity in cells infected with wild type or S.E-AvrA(+) strains. Therefore, Enteritidis AvrA-induced ZO-1 stability is achieved via suppression of the JNK pathway. Furthermore, the S.E-AvrA(-) strain led to enhanced bacterial invasion, both in vitro and in vivo. Taken together, our data reveal a novel role for AvrA in S. Enteritidis: Enteritidis AvrA stabilizes intestinal TJs and attenuates bacterial invasion. The manipulation of JNK activity and TJs in microbial-epithelial interactions may be a novel therapeutic approach for the treatment of infectious diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据