Boehm Manja, Simson Daniel, Escher Ulrike, Schmidt Anna-Maria, Bereswill Stefan, Tegtmeyer Nicole, Backert Steffen, Heimesaat Markus M
Department of Biology, Institute for Microbiology, Friedrich Alexander University Erlangen/Nuremberg, Staudtstr. 5, D-91058 Erlangen, Germany.
Department of Microbiology and Infection Immunology, Charité - University Medicine Berlin, Berlin, Germany.
Eur J Microbiol Immunol (Bp). 2018 Jul 17;8(3):70-77. doi: 10.1556/1886.2018.00011. eCollection 2018 Sep 28.
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. 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. 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 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.
是一种主要的食源性人畜共患病原体,导致很大比例的细菌性肠胃炎病例,以及吉兰 - 巴雷综合征和米勒 - 费希尔综合征。在感染期间,组织损伤主要由细菌侵入上皮细胞并穿越肠道屏障引起。能够进入固有层和血液,并可能转移到其他器官,如脾脏、肝脏或肠系膜淋巴结。然而,所涉及的分子机制尚未完全了解。主要通过使用丝氨酸蛋白酶高温需求A(HtrA)的细胞旁途径有效地穿过极化的肠道上皮细胞。然而,HtrA似乎具有双重功能,因为它在应激条件下还作为伴侣蛋白,与变性或错误折叠的周质蛋白相互作用。在这里,我们综述了HtrA在发病机制中的作用的最新进展。HtrA可以转运到细胞外空间并切割细胞间连接因子,如E - 钙黏蛋白以及可能的其他因子,破坏上皮屏障并使细菌能够进行细胞旁迁移。HtrA的分泌是其他病原体也采用的一种新发现的策略。因此,分泌的HtrA蛋白酶是极具吸引力的抗菌治疗靶点,并且可能为疫苗开发提供合适的候选物。