CPAF: a Chlamydial protease in search of an authentic substrate.
CPAF: a Chlamydial protease in search of an authentic substrate.
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DOI：
10.1371/journal.ppat.1002842
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Tan M
中科院分区：
文献类型：
--
作者：
Chen AL;Johnson KA;Lee JK;Sütterlin C;Tan M
衣原体属细菌是引起细胞内感染的主要人类病原体。衣原体蛋白水解酶CPAF被认为是一种重要的毒力因子，可以裂解或降解至少16种宿主蛋白，从而改变多种细胞过程。我们检查了11种已发表的CPAF底物，发现当CPAF活性在细胞处理过程中被抑制时，没有检测到蛋白质降解。我们表明，这些假定的CPAF底物的蛋白降解是由于细胞裂解产物中的酶活性，而不是在完整的细胞中。然而，衣原体感染的细胞表现出衣原体与宿主的相互作用，如高尔基重组、凋亡抵抗和宿主细胞骨架重塑，这些被归因于依赖CPAF的宿主蛋白的蛋白分解。我们的发现表明，其他机制可能负责这些衣原体与宿主的相互作用，并引起了人们对所有已发表的CPAF底物以及CPAF在衣原体致病中的作用的担忧。衣原体是一种入侵真核宿主细胞的细菌，生活在被称为衣原体包涵体的膜结合的隔间中。这些重要的人类和动物病原体的生长和生存依赖于与宿主细胞的广泛相互作用，这使得衣原体能够获得关键的营养物质，并避免宿主的抗微生物防御。衣原体被认为是通过被分泌到宿主细胞质中的衣原体蛋白酶CPAF裂解或降解宿主蛋白来引起许多宿主-病原体的相互作用。在这里，我们对这种毒力因子在感染过程中的拟议作用以及已发表的底物提出了质疑。我们发现，在衣原体感染的细胞中，没有检测到先前报道的11种CPAF底物的切割或降解，并且CPAF介导的这些宿主蛋白的蛋白分解发生在细胞收获和裂解过程中。然而，我们仍然观察到先前归因于CPAF蛋白分解这些蛋白的宿主-病原体相互作用，表明衣原体可能通过其他机制对宿主细胞造成这些影响。我们的发现要求重新评估所有已发表的CPAF底物，以及这种蛋白酶在衣原体发病中的拟议作用。
Bacteria in the genus Chlamydia are major human pathogens that cause an intracellular infection. A chlamydial protease, CPAF, has been proposed as an important virulence factor that cleaves or degrades at least 16 host proteins, thereby altering multiple cellular processes. We examined 11 published CPAF substrates and found that there was no detectable proteolysis when CPAF activity was inhibited during cell processing. We show that the reported proteolysis of these putative CPAF substrates was due to enzymatic activity in cell lysates rather than in intact cells. Nevertheless, Chlamydia-infected cells displayed Chlamydia-host interactions, such as Golgi reorganization, apoptosis resistance, and host cytoskeletal remodeling, that have been attributed to CPAF-dependent proteolysis of host proteins. Our findings suggest that other mechanisms may be responsible for these Chlamydia-host interactions, and raise concerns about all published CPAF substrates and the proposed roles of CPAF in chlamydial pathogenesis. Chlamydia are bacteria that invade eukaryotic host cells and live within a membrane-bound compartment called the chlamydial inclusion. Growth and survival of these important human and animal pathogens depends on extensive interactions with the host cell, which allow chlamydiae to acquire critical nutrients and to avoid host anti-microbial defenses. Chlamydiae are proposed to cause many of these host-pathogen interactions through the cleavage or degradation of host proteins by the chlamydial protease CPAF, which is secreted into the host cytoplasm. Here, we raise questions about the proposed roles of this virulence factor during infection, as well as its published substrates. We found that there was no detectable cleavage or degradation of 11 previously reported CPAF substrates in Chlamydia-infected cells and that CPAF-mediated proteolysis of these host proteins occurs during cell harvest and lysis. However, we still observed host-pathogen interactions previously attributed to CPAF proteolysis of these proteins, suggesting that Chlamydia is likely to cause these effects on the host cell through other mechanisms. Our findings call for a re-evaluation of all published CPAF substrates as well as the proposed roles of this protease in chlamydial pathogenesis.
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影响因子：
3.1
作者：
Dong, F;Su, H;Zhong, GM
通讯作者：
Zhong, GM
影响因子：
56.9
作者：
Horn, M;Collingro, A;Wagner, M
通讯作者：
Wagner, M
DOI：
10.1073/pnas.92.11.4877
发表时间：
1995-05-23
影响因子：
11.1
作者：
HACKSTADT, T;SCIDMORE, MA;ROCKEY, DD
通讯作者：
ROCKEY, DD
影响因子：
3.6
作者：
Dong, F;Pirbhai, M;Zhong, GM
通讯作者：
Zhong, GM
影响因子：
6.7
作者：
Christian JG;Heymann J;Paschen SA;Vier J;Schauenburg L;Rupp J;Meyer TF;Häcker G;Heuer D
通讯作者：
Heuer D