The Chlamydia protease CPAF regulates host and bacterial proteins to maintain pathogen vacuole integrity and promote virulence.
The Chlamydia protease CPAF regulates host and bacterial proteins to maintain pathogen vacuole integrity and promote virulence.
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DOI：
10.1016/j.chom.2011.06.008
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发表时间：
2011-07-21
影响因子：
30.3
通讯作者：
Valdivia RH
中科院分区：
文献类型：
--
作者：
Jorgensen I;Bednar MM;Amin V;Davis BK;Ting JP;McCafferty DG;Valdivia RH
专性细胞内细菌病原体沙眼衣原体（Chlamydia trachomatis）将许多效应蛋白注入上皮细胞的细胞质中，以操纵对细菌存活重要的宿主功能。此外，该细菌分泌丝氨酸蛋白酶，衣原体蛋白酶样活性因子（CPAF）。虽然有几个CPAF目标的报道，CPAF介导的蛋白水解的意义是不清楚的，由于缺乏具体的CPAF抑制剂和宿主靶点的多样性。我们报告说，CPAF还针对衣原体效应分泌早期在建立病原体的空泡（“包容”）。我们设计了一种细胞可渗透的CPAF特异性抑制肽，并使用它来确定CPAF通过降解进入预感染细胞期间易位的早期衣原体效应子来防止重复感染。长时间的CPAF抑制导致包涵体完整性的丧失和受感染上皮细胞的半胱天冬酶-1依赖性死亡。因此，CPAF在生态位保护，包含完整性和病原体存活方面发挥作用，使得CPAF特异性蛋白酶抑制剂的开发成为一种有吸引力的抗衣原体治疗策略。
The obligate intracellular bacterial pathogen Chlamydia trachomatis injects numerous effector proteins into the epithelial cell cytoplasm to manipulate host functions important for bacterial survival. In addition, the bacterium secretes a serine protease, chlamydial protease-like activity factor (CPAF). Although several CPAF targets are reported, the significance of CPAF-mediated proteolysis is unclear due to the lack of specific CPAF inhibitors and the diversity of host targets. We report that CPAF also targets chlamydial effectors secreted early during the establishment of the pathogen-containing vacuole (“inclusion”). We designed a cell-permeable CPAF-specific inhibitory peptide and used it to determine that CPAF prevents superinfection by degrading early Chlamydia effectors translocated during entry into a pre-infected cell. Prolonged CPAF inhibition leads to loss of inclusion integrity and caspase-1-dependent death of infected epithelial cells. Thus, CPAF functions in niche protection, inclusion integrity and pathogen survival, making the development of CPAF-specific protease inhibitors an attractive anti-chlamydial therapeutic strategy.
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影响因子：
3.6
作者：
Hower S;Wolf K;Fields KA
通讯作者：
Fields KA
DOI：
10.1084/jem.192.7.1035
发表时间：
2000-10-02
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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DOI：
10.1016/j.bbrc.2008.04.089
发表时间：
2008-06-27
影响因子：
3.1
作者：
Jewett, Travis J.;Dooley, Cheryl A.;Hackstadt, Ted
通讯作者：
Hackstadt, Ted