Bacterial protein AvrA stabilizes intestinal epithelial tight junctions via blockage of the C-Jun N-terminal kinase pathway Journal Article

Local Library Link: Find It @ Loyola

Authors: Zhang, Y; Wu, S.; Ma, J.; Xia, Y.; Ai, X; Sun, J
Article Title: Bacterial protein AvrA stabilizes intestinal epithelial tight junctions via blockage of the C-Jun N-terminal kinase pathway
Abstract: The Salmonella type III secretory system secretes virulence proteins, called effectors. Effectors are responsible for the alteration of tight junctions (TJ) and epithelial functions in intestinal infection and inflammation. In a previous study, we have demonstrated that a bacterial effector AvrA plays a role in stabilizing TJs and balancing the opposing action of other bacterial effectors. However, the molecular mechanisms by which AvrA-modulates TJ protein expression remain unknown. AvrA possesses acetyltransferase activity toward specific mitogen-activated protein kinase kinases (MAPKKs) and potently inhibits the c-Jun N-terminal kinase (JNK) pathway in inflammation. Inhibition of the JNK pathway is known to inhibit the TJ protein disassemble. Therefore, we hypothesize that AvrA stabilizes intestinal epithelial TJs via c-Jun and JNK pathway blockage. Using both in vitro and in vivo models, we showed that AvrA targets the c-Jun and JNK pathway that in turn stabilizes TJ protein ZO-1. Inhibition of JNK abolished the effect of AvrA on ZO-1. We further determined that AvrA suppressed the transcription factor activator protein-1, which was regulated by activated JNK. Moreover, we identified the functional domain of AvrA that directly regulated TJs using a series of AvrA mutants. The role of AvrA represents a highly refined bacterial strategy that helps the bacteria survive in the host and dampens the inflammatory response of the host. Our findings have uncovered a novel role of the bacterial protein AvrA in suppressing the inflammatory response of the host through JNK-regulated blockage of epithelial cell barrier function.
Journal Title: Tissue barriers
Volume: 3
Issue: 1-2
ISSN: 2168-8362; 2168-8362
Publisher: Unknown  
Journal Place: United States
Date Published: 2015
Start Page: e972849
Language: eng
DOI/URL:

10.4161/21688362.2014.972849
Notes: LR: 20150417; GR: R01 HL113640/HL/NHLBI NIH HHS/United States; JID: 101601065; OID: NLM: PMC4372022 [Available on 12/31/15]; OTO: NOTNLM; PMCR: 2015/12/31 00:00; 2015 [ecollection]; 2014/08/15 [received]; 2014/09/27 [accepted]; 2015/04/03 [epublish]; epublish