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

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 th...

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Autores principales: Wang, Hao, Lv, Long-Bao, Chen, Li-Ping, Xiao, Jin-Long, Shen, Jue, Gao, Bin, Zhao, Jin-Gang, Han, Dong-Mei, Chen, Bin-Xun, Wang, Shuai, Liu, Gen, Xin, Ai-Guo, Xiao, Peng, Gao, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058142/
https://www.ncbi.nlm.nih.gov/pubmed/36977062
http://dx.doi.org/10.3390/toxins15030171
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author Wang, Hao
Lv, Long-Bao
Chen, Li-Ping
Xiao, Jin-Long
Shen, Jue
Gao, Bin
Zhao, Jin-Gang
Han, Dong-Mei
Chen, Bin-Xun
Wang, Shuai
Liu, Gen
Xin, Ai-Guo
Xiao, Peng
Gao, Hong
author_facet Wang, Hao
Lv, Long-Bao
Chen, Li-Ping
Xiao, Jin-Long
Shen, Jue
Gao, Bin
Zhao, Jin-Gang
Han, Dong-Mei
Chen, Bin-Xun
Wang, Shuai
Liu, Gen
Xin, Ai-Guo
Xiao, Peng
Gao, Hong
author_sort Wang, Hao
collection PubMed
description 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.
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spelling pubmed-100581422023-03-30 Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis Wang, Hao Lv, Long-Bao Chen, Li-Ping Xiao, Jin-Long Shen, Jue Gao, Bin Zhao, Jin-Gang Han, Dong-Mei Chen, Bin-Xun Wang, Shuai Liu, Gen Xin, Ai-Guo Xiao, Peng Gao, Hong Toxins (Basel) Article 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. MDPI 2023-02-22 /pmc/articles/PMC10058142/ /pubmed/36977062 http://dx.doi.org/10.3390/toxins15030171 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Hao
Lv, Long-Bao
Chen, Li-Ping
Xiao, Jin-Long
Shen, Jue
Gao, Bin
Zhao, Jin-Gang
Han, Dong-Mei
Chen, Bin-Xun
Wang, Shuai
Liu, Gen
Xin, Ai-Guo
Xiao, Peng
Gao, Hong
Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis
title Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis
title_full Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis
title_fullStr Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis
title_full_unstemmed Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis
title_short Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis
title_sort hemolysin co-regulatory protein 1 enhances the virulence of clinically isolated escherichia coli in km mice by increasing inflammation and inducing pyroptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058142/
https://www.ncbi.nlm.nih.gov/pubmed/36977062
http://dx.doi.org/10.3390/toxins15030171
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