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Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway.

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.

SUBMITTER: Lin Z

PROVIDER: S-EPMC5207190 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway.

Lin Zhijie Z Zhang Yong-Guo YG Xia Yinglin Y Xu Xiulong X Jiao Xinan X Sun Jun J

The Journal of biological chemistry 20161115 52

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 v ...[more]

PMID: 27875307

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Project description:BackgroundIn the current context of reduced and limited antibiotic use, several pathogens and stressors cause intestinal oxidative stress in poultry, which leads to a reduced feed intake, slow or stagnant growth and development, and even death, resulting in huge economic losses to the poultry breeding industry. Oxidative stress in animals is a non-specific injury for which no targeted drug therapy is available; however, the health of poultry can be improved by adding appropriate feed additives. Bacillus pumilus, as a feed additive, promotes growth and development and reduces intestinal oxidative stress damage in poultry. Heat shock protein 70 (HSP70) senses oxidative damage and repairs unfolded and misfolded proteins; its protective effect has been widely investigated. Mitogen-activated protein kinase/protein kinase C (MAPK/PKC) and hypoxia inducible factor-1 alpha (HIF-1α) are also common proteins associated with inflammatory response induced by several stressors, but there is limited research on these proteins in the context of poultry intestinal Salmonella Enteritidis (SE) infections. In the present study, we isolated a novel strain of Bacillus pumilus with excellent performance from the feces of healthy yaks, named TS1. To investigate the effect of TS1 on SE-induced enteritis in broilers, 120 6-day-old white-feathered broilers were randomly divided into four groups (con, TS1, SE, TS1 + SE). TS1 and TS1 + SE group chickens were fed with 1.4 × 107 colony-forming units per mL of TS1 for 15 days and intraperitoneally injected with SE to establish the oxidative stress model. Then, we investigated whether TS1 protects the intestine of SE-treated broiler chickens using inflammatory cytokine gene expression analysis, stress protein quantification, antioxidant quantification, and histopathological analysis.ResultsThe TS1 + SE group showed lower MDA and higher GSH-Px, SOD, and T-AOC than the SE group. TS1 alleviated the effects of SE on intestinal villus length and crypt depth. Our results suggest that SE exposure increased the expression of inflammatory factors (IL-1β, IL-6, TNF-α, IL-4, and MCP-1), p38 MAPK, and PKCβ and decreased the expression of HSP60, HSP70, and HIF-1α, whereas TS1 alleviated these effects.ConclusionsBacillus pumilus TS1 alleviated oxidative stress damage caused by SE and attenuated the inflammatory response in broilers through MAPK/PKC regulation of HSPs/HIF-1α.

Dataset Information

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway.

Publications

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway.

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