Back to Search Start Over

Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis

Authors :
Hao Wang
Long-Bao Lv
Li-Ping Chen
Jin-Long Xiao
Jue Shen
Bin Gao
Jin-Gang Zhao
Dong-Mei Han
Bin-Xun Chen
Shuai Wang
Gen Liu
Ai-Guo Xin
Peng Xiao
Hong Gao
Source :
Toxins, Vol 15, Iss 3, p 171 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Hemolysin-coregulated protein 1 (Hcp1) is an effector released by the type VI secretion system (T6SS) in certain pathogenic strains of Escherichia coli (E. coli) that causes apoptosis and contributes to the development of meningitis. The exact toxic consequences of Hcp1 and whether it intensifies the inflammatory response by triggering pyroptosis are yet unknown. Here, utilizing the CRISPR/Cas9 genome editing method, we removed the gene expressing Hcp1 from wild-type E. coli W24 and examined the impact of Hcp1 on E. coli virulence in Kunming (KM) mice. It was found that Hcp1-sufficient E. coli was more lethal, exacerbating acute liver injury (ALI) and acute kidney injury (AKI) or even systemic infections, structural organ damage, and inflammatory factor infiltration. These symptoms were alleviated in mice infected with W24Δhcp1. Additionally, we investigated the molecular mechanism by which Hcp1 worsens AKI and found that pyroptosis is involved, manifested as DNA breaks in many renal tubular epithelial cells. Genes or proteins closely related to pyroptosis are abundantly expressed in the kidney. Most importantly, Hcp1 promotes the activation of the NLRP3 inflammasome and the expression of active caspase-1, thereby cleaving GSDMD-N and accelerating the release of active IL-1β and ultimately leading to pyroptosis. In conclusion, Hcp1 enhances the virulence of E. coli, aggravates ALI and AKI, and promotes the inflammatory response; moreover, Hcp1-induced pyroptosis is one of the molecular mechanisms of AKI.

Details

Language :
English
ISSN :
20726651
Volume :
15
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Toxins
Publication Type :
Academic Journal
Accession number :
edsdoj.faea309f6ca84378bc408ef1bea65e7d
Document Type :
article
Full Text :
https://doi.org/10.3390/toxins15030171