Chronic effects of a Salmonella type III secretion effector protein AvrA in vivo.
BACKGROUND
Salmonella infection is a common public health problem that can become chronic and increase the risk of inflammatory bowel diseases and cancer. AvrA is a Salmonella bacterial type III secretion effector protein. Increasing evidence demonstrates that AvrA is a multi-functional enzyme with critical roles in inhibiting inflammation, regulating apoptosis, and enhancing proliferation. However, the chronic effects of Salmonella and effector AvrA in vivo are still unknown. Moreover, alive, mutated, non-invasive Salmonella is used as a vector to specifically target cancer cells. However, studies are lacking on chronic infection with non-pathogenic or mutated Salmonella in the host.


RESULTS
We infected mice with Salmonella Typhimurium for 27 weeks and investigated the physiological effects as well as the role of AvrA in intestinal inflammation. We found altered body weight, intestinal pathology, and bacterial translocation in spleen, liver, and gallbladder in chronically Salmonella-infected mice. Moreover, AvrA suppressed intestinal inflammation and inhibited the secretion of cytokines IL-12, IFN-gamma, and TNF-alpha. AvrA expression in Salmonella enhanced its invasion ability. Liver abscess and Salmonella translocation in the gallbladder were observed and may be associated with AvrA expression in Salmonella.


CONCLUSIONS
We created a mouse model with persistent Salmonella infection in vivo. Our study further emphasizes the importance of the Salmonella effector protein AvrA in intestinal inflammation, bacterial translocation, and chronic infection in vivo.
Lu
Rong
R
Department of Medicine, University of Rochester, Rochester, New York, United States of America.
Wu
Shaoping
S
Liu
Xingyin
X
Xia
Yinglin
Y
Zhang
Yong-Guo
YG
Sun
Jun
J
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005704:Gallbladder / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009068:Movement / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity / Q000187:drug effects; D012480:Salmonella Infections / Q000382:microbiology / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D013307:Streptomycin / Q000494:pharmacology; D016019:Survival Analysis; D015430:Weight Gain / Q000187:drug effects
C487891:AvrA protein, Salmonella typhimurium; D001426:Bacterial Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D013307:Streptomycin
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