{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:27:23Z","timestamp":1789424843550,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31960692"],"award-info":[{"award-number":["31960692"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31660704"],"award-info":[{"award-number":["31660704"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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 W24\u0394hcp1. 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-1\u03b2 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.<\/jats:p>","DOI":"10.3390\/toxins15030171","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T04:33:56Z","timestamp":1677040436000},"page":"171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1555-7261","authenticated-orcid":false,"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Bao","family":"Lv","sequence":"additional","affiliation":[{"name":"National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ping","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Foreign Languages, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Long","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Shen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Gang","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Mei","family":"Han","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin-Xun","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Guo","family":"Xin","sequence":"additional","affiliation":[{"name":"National Foot-and-Mouth Disease Para-Reference Laboratory (Kunming), Yunnan Animal Science and Veterinary Institute, Kunming 650224, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1126\/science.1128393","article-title":"A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus","volume":"312","author":"Mougous","year":"2006","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.chom.2017.05.004","article-title":"Shigella sonnei Encodes a Functional T6SS Used for Interbacterial Competition and Niche Occupancy","volume":"21","author":"Anderson","year":"2017","journal-title":"Cell Host 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