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Yersiniabactin-Producing E. coli Induces the Pyroptosis of Intestinal Epithelial Cells via the NLRP3 Pathway and Promotes Gut Inflammation
Wang, H; Shan, CL; Gao, B; Xiao, JL; Shen, J; Zhao, JG; Han, DM; Chen, BX; Wang, S; Liu, G; Xin, AG; Lv, LB; Xiao, P; Gao, H
2023
发表期刊INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN1661-6596
卷号24期号:14
摘要The high-pathogenicity island (HPI) was initially identified in Yersinia and can be horizontally transferred to Escherichia coli to produce yersiniabactin (Ybt), which enhances the pathogenicity of E. coli by competing with the host for Fe3+. Pyroptosis is gasdermin-induced necrotic cell death. It involves the permeabilization of the cell membrane and is accompanied by an inflammatory response. It is still unclear whether Ybt HPI can cause intestinal epithelial cells to undergo pyroptosis and contribute to gut inflammation during E. coli infection. In this study, we infected intestinal epithelial cells of mice with E. coli ZB-1 and the Ybt-deficient strain ZB-1 & UDelta;irp2. Our findings demonstrate that Ybt-producing E. coli is more toxic and exacerbates gut inflammation during systemic infection. Mechanistically, our results suggest the involvement of the NLRP3/caspase-1/GSDMD pathway in E. coli infection. Ybt promotes the assembly and activation of the NLRP3 inflammasome, leading to GSDMD cleavage into GSDMD-N and promoting the pyroptosis of intestinal epithelial cells, ultimately aggravating gut inflammation. Notably, NLRP3 knockdown alleviated these phenomena, and the binding of free Ybt to NLRP3 may be the trigger. Overall, our results show that Ybt HPI enhances the pathogenicity of E. coli and induces pyroptosis via the NLRP3 pathway, which is a new mechanism through which E. coli promotes gut inflammation. Furthermore, we screened drugs targeting NLRP3 from an existing drug library, providing a list of potential drug candidates for the treatment of gut injury caused by E. coli.
收录类别SCI
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/14397
专题管理、支撑部门_实验动物中心
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GB/T 7714
Wang, H,Shan, CL,Gao, B,et al. Yersiniabactin-Producing E. coli Induces the Pyroptosis of Intestinal Epithelial Cells via the NLRP3 Pathway and Promotes Gut Inflammation[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2023,24(14).
APA Wang, H.,Shan, CL.,Gao, B.,Xiao, JL.,Shen, J.,...&Gao, H.(2023).Yersiniabactin-Producing E. coli Induces the Pyroptosis of Intestinal Epithelial Cells via the NLRP3 Pathway and Promotes Gut Inflammation.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,24(14).
MLA Wang, H,et al."Yersiniabactin-Producing E. coli Induces the Pyroptosis of Intestinal Epithelial Cells via the NLRP3 Pathway and Promotes Gut Inflammation".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24.14(2023).
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