Psonis John J, Thanassi David G
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794.
Center for Infectious Diseases, Stony Brook University, Stony Brook, NY 11794.
EcoSal Plus. 2019 Mar;8(2). doi: 10.1128/ecosalplus.ESP-0033-2018.
The chaperone-usher (CU) pathway is a conserved secretion system dedicated to the assembly of a superfamily of virulence-associated surface structures by a wide range of Gram-negative bacteria. Pilus biogenesis by the CU pathway requires two specialized assembly components: a dedicated periplasmic chaperone and an integral outer membrane assembly and secretion platform termed the usher. The CU pathway assembles a variety of surface fibers, ranging from thin, flexible filaments to rigid, rod-like organelles. Pili typically act as adhesins and function as virulence factors that mediate contact with host cells and colonization of host tissues. Pilus-mediated adhesion is critical for early stages of infection, allowing bacteria to establish a foothold within the host. Pili are also involved in modulation of host cell signaling pathways, bacterial invasion into host cells, and biofilm formation. Pili are critical for initiating and sustaining infection and thus represent attractive targets for the development of antivirulence therapeutics. Such therapeutics offer a promising alternative to broad-spectrum antibiotics and provide a means to combat antibiotic resistance and treat infection while preserving the beneficial microbiota. A number of strategies have been taken to develop antipilus therapeutics, including vaccines against pilus proteins, competitive inhibitors of pilus-mediated adhesion, and small molecules that disrupt pilus biogenesis. Here we provide an overview of the function and assembly of CU pili and describe current efforts aimed at interfering with these critical virulence structures.
伴侣-外膜蛋白（CU）途径是一种保守的分泌系统，广泛存在于革兰氏阴性菌中，用于组装一系列与毒力相关的表面结构超家族。通过CU途径进行菌毛生物合成需要两个专门的组装组件：一个专用的周质伴侣蛋白和一个称为外膜蛋白的完整外膜组装和分泌平台。CU途径可组装各种表面纤维，从细的、柔韧的细丝到刚性的、杆状细胞器。菌毛通常作为粘附素，作为毒力因子发挥作用，介导与宿主细胞的接触以及在宿主组织中的定殖。菌毛介导的粘附对于感染的早期阶段至关重要，使细菌能够在宿主体内立足。菌毛还参与调节宿主细胞信号通路、细菌侵入宿主细胞以及生物膜形成。菌毛对于引发和维持感染至关重要，因此是抗毒力疗法开发的有吸引力的靶点。此类疗法为广谱抗生素提供了一种有前景的替代方案，并提供了一种对抗抗生素耐药性和治疗感染同时保留有益微生物群的方法。已经采取了多种策略来开发抗菌毛疗法，包括针对菌毛蛋白的疫苗、菌毛介导粘附的竞争性抑制剂以及破坏菌毛生物合成的小分子。在这里，我们概述了CU菌毛的功能和组装，并描述了目前针对干扰这些关键毒力结构所做的努力。
