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蛋白酶在生活方式和发病机制中的进化和作用。

Evolution and Role of Proteases in Lifestyle and Pathogenesis.

机构信息

Department of Biology, Division of Microbiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.

出版信息

Biomolecules. 2023 Feb 8;13(2):323. doi: 10.3390/biom13020323.

Abstract

Infection with the main human food-borne pathogen causes campylobacteriosis that accounts for a substantial percentage of gastrointestinal infections. The disease usually manifests as diarrhea that lasts for up to two weeks. possesses an array of peptidases and proteases that are critical for its lifestyle and pathogenesis. These include serine proteases Cj1365c, Cj0511 and HtrA; AAA+ group proteases ClpP, Lon and FtsH; and zinc-dependent protease PqqE, proline aminopeptidase PepP, oligopeptidase PepF and peptidase C26. Here, we review the numerous critical roles of these peptide bond-dissolving enzymes in cellular processes of that include protein quality control; protein transport across the inner and outer membranes into the periplasm, cell surface or extracellular space; acquisition of amino acids and biofilm formation and dispersal. In addition, we highlight their role as virulence factors that inflict intestinal tissue damage by promoting cell invasion and mediating cleavage of crucial host cell factors such as epithelial cell junction proteins. Furthermore, we reconstruct the evolution of these proteases in 34 species of the genus. Finally, we discuss to what extent proteases have initiated the search for inhibitor compounds as prospective novel anti-bacterial therapies.

摘要

感染主要的人类食源性病原体 会导致弯曲菌病,占胃肠道感染的很大比例。这种疾病通常表现为持续长达两周的腹泻。 拥有一系列的肽酶和蛋白酶,这些酶对其生活方式和发病机制至关重要。其中包括丝氨酸蛋白酶 Cj1365c、Cj0511 和 HtrA;AAA+ 组蛋白酶 ClpP、Lon 和 FtsH;以及锌依赖性蛋白酶 PqqE、脯氨酸氨肽酶 PepP、寡肽酶 PepF 和肽酶 C26。在这里,我们回顾了这些肽键溶解酶在 细胞过程中的许多关键作用,包括蛋白质质量控制;蛋白质穿过内膜和外膜进入周质、细胞表面或细胞外空间的运输;氨基酸的获取和生物膜的形成和分散。此外,我们强调了它们作为毒力因子的作用,通过促进细胞入侵和介导关键宿主细胞因子如上皮细胞连接蛋白的切割,导致肠道组织损伤。此外,我们重建了 34 种 属中这些蛋白酶的进化。最后,我们讨论了弯曲杆菌蛋白酶在多大程度上引发了寻找抑制剂化合物作为潜在新型抗菌治疗方法的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/9953165/514342f5c902/biomolecules-13-00323-g001.jpg

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