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A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF
Urogenital Chlamydia trachomatis infection is one of the most common bacterial sexually transmitted diseases globally. Untreated C. trachomatis infections can ascend to the upper genital tract and establish a series of severe complications. Previous studies using C3(−/−) and C5(−/−) mice models demo...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787135/ https://www.ncbi.nlm.nih.gov/pubmed/35087765 http://dx.doi.org/10.3389/fcimb.2021.732163 |
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author | Peng, Liang Gao, Jingping Hu, Zihao Zhang, Hongbo Tang, Lingli Wang, Fuyan Cui, Lei Liu, Shanshan Zhao, Yujie Xu, Hong Su, Xin Feng, Xiaojing Fang, Yiyuan Chen, Jianlin |
author_facet | Peng, Liang Gao, Jingping Hu, Zihao Zhang, Hongbo Tang, Lingli Wang, Fuyan Cui, Lei Liu, Shanshan Zhao, Yujie Xu, Hong Su, Xin Feng, Xiaojing Fang, Yiyuan Chen, Jianlin |
author_sort | Peng, Liang |
collection | PubMed |
description | Urogenital Chlamydia trachomatis infection is one of the most common bacterial sexually transmitted diseases globally. Untreated C. trachomatis infections can ascend to the upper genital tract and establish a series of severe complications. Previous studies using C3(−/−) and C5(−/−) mice models demonstrated that C3-independent activation of C5 occurred during C. trachomatis infection. However, the mechanism of how chlamydial infection activates C5 in the absence of C3 has yet to be elucidated. To delineate interactions between C5 and chlamydial infection, cleavage products in a co-incubation system containing purified human C5 and C. trachomatis-HeLa229 cell lysates were analyzed, and a novel cleavage pattern of C5 activation induced by C. trachomatis infection was identified. C5 was cleaved efficiently at the previously unidentified site K970, but was cleaved poorly at site R751. C5b was modified to C5b(Ct), which later formed C5b(Ct)-9, which had enhanced lytic ability compared with C5b-9. The chlamydial serine protease CPAF contributed to C3-independent C5 activation during C. trachomatis infection. Nafamostat mesylate, a serine protease inhibitor with a good safety profile, had a strong inhibitory effect on C5 activation induced by chlamydial infection. These discoveries reveal the mechanism of C3-independent C5 activation induced by chlamydial infection, and furthermore provide a potential therapeutic target and drug for preventing tubal fibrosis caused by chlamydial infection. |
format | Online Article Text |
id | pubmed-8787135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87871352022-01-26 A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF Peng, Liang Gao, Jingping Hu, Zihao Zhang, Hongbo Tang, Lingli Wang, Fuyan Cui, Lei Liu, Shanshan Zhao, Yujie Xu, Hong Su, Xin Feng, Xiaojing Fang, Yiyuan Chen, Jianlin Front Cell Infect Microbiol Cellular and Infection Microbiology Urogenital Chlamydia trachomatis infection is one of the most common bacterial sexually transmitted diseases globally. Untreated C. trachomatis infections can ascend to the upper genital tract and establish a series of severe complications. Previous studies using C3(−/−) and C5(−/−) mice models demonstrated that C3-independent activation of C5 occurred during C. trachomatis infection. However, the mechanism of how chlamydial infection activates C5 in the absence of C3 has yet to be elucidated. To delineate interactions between C5 and chlamydial infection, cleavage products in a co-incubation system containing purified human C5 and C. trachomatis-HeLa229 cell lysates were analyzed, and a novel cleavage pattern of C5 activation induced by C. trachomatis infection was identified. C5 was cleaved efficiently at the previously unidentified site K970, but was cleaved poorly at site R751. C5b was modified to C5b(Ct), which later formed C5b(Ct)-9, which had enhanced lytic ability compared with C5b-9. The chlamydial serine protease CPAF contributed to C3-independent C5 activation during C. trachomatis infection. Nafamostat mesylate, a serine protease inhibitor with a good safety profile, had a strong inhibitory effect on C5 activation induced by chlamydial infection. These discoveries reveal the mechanism of C3-independent C5 activation induced by chlamydial infection, and furthermore provide a potential therapeutic target and drug for preventing tubal fibrosis caused by chlamydial infection. Frontiers Media S.A. 2022-01-11 /pmc/articles/PMC8787135/ /pubmed/35087765 http://dx.doi.org/10.3389/fcimb.2021.732163 Text en Copyright © 2022 Peng, Gao, Hu, Zhang, Tang, Wang, Cui, Liu, Zhao, Xu, Su, Feng, Fang and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology Peng, Liang Gao, Jingping Hu, Zihao Zhang, Hongbo Tang, Lingli Wang, Fuyan Cui, Lei Liu, Shanshan Zhao, Yujie Xu, Hong Su, Xin Feng, Xiaojing Fang, Yiyuan Chen, Jianlin A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF |
title | A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF |
title_full | A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF |
title_fullStr | A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF |
title_full_unstemmed | A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF |
title_short | A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF |
title_sort | novel cleavage pattern of complement c5 induced by chlamydia trachomatis infection via the chlamydial protease cpaf |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787135/ https://www.ncbi.nlm.nih.gov/pubmed/35087765 http://dx.doi.org/10.3389/fcimb.2021.732163 |
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