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Recombinant Salmonella expressing SspH2-EscI fusion protein limits its colonization in mice.


ABSTRACT:

Background

Activation of inflammasome contributes to the clearance of intracellular bacteria. C-terminus of E. coli EscI protein can activate NLRC4 (NLR family, CARD domain containing-4) inflammasome in macrophages. The purpose of this study was to determine if activation of NLRC4 inflammasome by EscI can reduce the colonization of Salmonella in mice.

Results

A recombinant S. typhimurium strain expressing fusion protein of the N-terminal SspH2 (a Salmonella type III secretion system 2 effector) and C-terminal EscI was constructed and designated as X4550(pYA3334-SspH2-EscI). In vitro assay showed that X4550(pYA3334-SspH2-EscI) significantly enhanced IL-1β and IL-18 secretion (P < 0.05) and pyroptotic cell death of mouse peritoneal macrophages, compared with those infected with control strain, X4550(pYA3334-SspH2). In vivo studies showed that colonization of X4550(pYA3334-SspH2-EscI) in both spleen and liver were significantly lower than that of X4550(pYA3334-SspH2) (P < 0.05). The bacterial counts of X4550(pYA3334-SspH2-EscI) in mice decreased, while those of X4550(pYA3334-SspH2) increased over the time after infection. Additionally, X4550(pYA3334-SspH2-EscI) induced a less pathological alteration in spleen and liver than X4550(pYA3334-SspH2).

Conclusion

Fusion protein SspH2-EscI may be translocated into macrophages and activate NLRC4 inflammasome, which limits Salmonella colonization in spleen and liver of mice.

SUBMITTER: Hu M 

PROVIDER: S-EPMC5415771 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Recombinant Salmonella expressing SspH2-EscI fusion protein limits its colonization in mice.

Hu Maozhi M   Zhao Weixin W   Gao Wei W   Li Wenhua W   Meng Chuang C   Yan Qiuxiang Q   Wang Yuyang Y   Zhou Xiaohui X   Geng Shizhong S   Pan Zhiming Z   Cui Guiyou G   Jiao Xinan X  

BMC immunology 20170503 1


<h4>Background</h4>Activation of inflammasome contributes to the clearance of intracellular bacteria. C-terminus of E. coli EscI protein can activate NLRC4 (NLR family, CARD domain containing-4) inflammasome in macrophages. The purpose of this study was to determine if activation of NLRC4 inflammasome by EscI can reduce the colonization of Salmonella in mice.<h4>Results</h4>A recombinant S. typhimurium strain expressing fusion protein of the N-terminal SspH2 (a Salmonella type III secretion syst  ...[more]

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