Function of Serine Protease HtrA in the Lifecycle of the Foodborne Pathogen Campylobacter jejuni.
Function of Serine Protease HtrA in the Lifecycle of the Foodborne Pathogen Campylobacter jejuni.
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DOI：
10.1556/1886.2018.00011
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发表时间：
2018-09-28
影响因子：
2.2
通讯作者：
Heimesaat MM
中科院分区：
文献类型：
--
作者：
Boehm M;Simson D;Escher U;Schmidt AM;Bereswill S;Tegtmeyer N;Backert S;Heimesaat MM
空肠弯曲菌是一种主要的食源性人畜共患病原体，可引起很大比例的细菌性胃肠炎病例，以及格林-巴利综合征和米勒-费希尔综合征。在感染过程中，组织损伤主要是由细菌侵入上皮细胞并穿过肠屏障引起的。C.空肠能够进入固有层和血流，并且可以移动到其它器官，例如脾、肝或肠系膜淋巴结。然而，所涉及的分子机制尚未完全了解。C.空肠可以有效地穿越极化的肠上皮细胞，主要是通过使用丝氨酸蛋白酶高温要求A（HtrA）的细胞旁途径。然而，似乎HtrA具有双重功能，因为它还充当伴侣，在胁迫条件下与变性或错误折叠的周质蛋白相互作用。本文就HtrA在C.空肠发病机制HtrA可以被转运到细胞外空间并切割细胞与细胞的连接因子，如E-钙粘蛋白和可能的其他因子，破坏上皮屏障并使细菌能够进行细胞旁迁移。HtrA的分泌是一种新发现的策略，也被其他病原体利用。因此，分泌的HtrA蛋白酶代表了抗细菌治疗的高度有吸引力的靶标，并且可以为疫苗开发提供合适的候选物。
Campylobacter jejuni is a major food-borne zoonotic pathogen, responsible for a large proportion of bacterial gastroenteritis cases, as well as Guillian-Barré and Miller-Fisher syndromes. During infection, tissue damage is mainly caused by bacteria invading epithelial cells and traversing the intestinal barrier. C. jejuni is able to enter the lamina propria and the bloodstream and may move into other organs, such as spleen, liver, or mesenteric lymph nodes. However, the involved molecular mechanisms are not fully understood. C. jejuni can transmigrate effectively across polarized intestinal epithelial cells mainly by the paracellular route using the serine protease high-temperature requirement A (HtrA). However, it appears that HtrA has a dual function, as it also acts as a chaperone, interacting with denatured or misfolded periplasmic proteins under stress conditions. Here, we review recent progress on the role of HtrA in C. jejuni pathogenesis. HtrA can be transported into the extracellular space and cleaves cell-to-cell junction factors, such as E-cadherin and probably others, disrupting the epithelial barrier and enabling paracellular transmigration of the bacteria. The secretion of HtrA is a newly discovered strategy also utilized by other pathogens. Thus, secreted HtrA proteases represent highly attractive targets for anti-bacterial treatment and may provide a suitable candidate for vaccine development.