Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway
Year: 2016
Type: article
Abstract: 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.
Source: Journal of Biological Chemistry
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: G1265615842, G4235399637, G9000053883
OpenAlex ID: W2553357491