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ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model
Colibactin is a complex secondary metabolite that leads to genotoxicity that interferes with the eukaryotic cell cycle. It plays an important role in many diseases, including neonatal mouse sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) is responsible for several diseases in the pou...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402462/ https://www.ncbi.nlm.nih.gov/pubmed/34437417 http://dx.doi.org/10.3390/toxins13080546 |
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author | Wang, Peili Zhang, Jiaxiang Chen, Yanfei Zhong, Haoran Wang, Heng Li, Jianji Zhu, Guoqiang Xia, Pengpeng Cui, Luying Li, Jun Dong, Junsheng Gao, Qingqing Meng, Xia |
author_facet | Wang, Peili Zhang, Jiaxiang Chen, Yanfei Zhong, Haoran Wang, Heng Li, Jianji Zhu, Guoqiang Xia, Pengpeng Cui, Luying Li, Jun Dong, Junsheng Gao, Qingqing Meng, Xia |
author_sort | Wang, Peili |
collection | PubMed |
description | Colibactin is a complex secondary metabolite that leads to genotoxicity that interferes with the eukaryotic cell cycle. It plays an important role in many diseases, including neonatal mouse sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) is responsible for several diseases in the poultry industry and may threaten human health due to its potential zoonosis. In this study, we confirmed that clbG was necessary for the APEC XM strain to produce colibactin. The deletion of clbG on APEC XM contributed to lowered γH2AX expression, no megalocytosis, and no cell cycle arrest in vitro. None of the 4-week Institute of Cancer Research mice infected with the APEC XM ΔclbG contracted meningitis or displayed weakened clinical symptoms. Fewer histopathological lesions were observed in the APEC XM ΔclbG group. The bacterial colonization of tissues and the relative expression of cytokines (IL-1β, IL-6, and TNF-α) in the brains decreased significantly in the APEC XM ΔclbG group compared to those in the APEC XM group. The tight junction proteins (claudin-5, occludin, and ZO-1) were not significantly destroyed in APEC XM ΔclbG group in vivo and in vitro. In conclusion, clbG is necessary for the synthesis of the genotoxin colibactin and affects the development of APEC meningitis in mice. |
format | Online Article Text |
id | pubmed-8402462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84024622021-08-29 ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model Wang, Peili Zhang, Jiaxiang Chen, Yanfei Zhong, Haoran Wang, Heng Li, Jianji Zhu, Guoqiang Xia, Pengpeng Cui, Luying Li, Jun Dong, Junsheng Gao, Qingqing Meng, Xia Toxins (Basel) Article Colibactin is a complex secondary metabolite that leads to genotoxicity that interferes with the eukaryotic cell cycle. It plays an important role in many diseases, including neonatal mouse sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) is responsible for several diseases in the poultry industry and may threaten human health due to its potential zoonosis. In this study, we confirmed that clbG was necessary for the APEC XM strain to produce colibactin. The deletion of clbG on APEC XM contributed to lowered γH2AX expression, no megalocytosis, and no cell cycle arrest in vitro. None of the 4-week Institute of Cancer Research mice infected with the APEC XM ΔclbG contracted meningitis or displayed weakened clinical symptoms. Fewer histopathological lesions were observed in the APEC XM ΔclbG group. The bacterial colonization of tissues and the relative expression of cytokines (IL-1β, IL-6, and TNF-α) in the brains decreased significantly in the APEC XM ΔclbG group compared to those in the APEC XM group. The tight junction proteins (claudin-5, occludin, and ZO-1) were not significantly destroyed in APEC XM ΔclbG group in vivo and in vitro. In conclusion, clbG is necessary for the synthesis of the genotoxin colibactin and affects the development of APEC meningitis in mice. MDPI 2021-08-06 /pmc/articles/PMC8402462/ /pubmed/34437417 http://dx.doi.org/10.3390/toxins13080546 Text en © 2021 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, Peili Zhang, Jiaxiang Chen, Yanfei Zhong, Haoran Wang, Heng Li, Jianji Zhu, Guoqiang Xia, Pengpeng Cui, Luying Li, Jun Dong, Junsheng Gao, Qingqing Meng, Xia ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model |
title | ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model |
title_full | ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model |
title_fullStr | ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model |
title_full_unstemmed | ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model |
title_short | ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model |
title_sort | clbg in avian pathogenic escherichia coli contributes to meningitis development in a mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402462/ https://www.ncbi.nlm.nih.gov/pubmed/34437417 http://dx.doi.org/10.3390/toxins13080546 |
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