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

Maozhi Hu, Weixin Zhao, Wei Gao, Wenhua Li, Chuang Meng, Qiuxiang Yan, Yuyang Wang, Xiaohui Zhou, Shizhong Geng, Zhiming Pan, Guiyou Cui, Xinan Jiao
<span title="2017-05-03">2017</span> <i title="Springer Nature"> <a target="_blank" rel="noopener" href="" style="color: black;">BMC Immunology</a> </i> &nbsp;
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
more &raquo; ... inal 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.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.1186/s12865-017-0203-2</a> <a target="_blank" rel="external noopener" href="">pmid:28468643</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC5415771</a> <a target="_blank" rel="external noopener" href="">fatcat:ujpf7br3dfa37b2ko4mtlpvgmm</a> </span>
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