Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23219, USA.
Biomolecules. 2021 Feb 19;11(2):316. doi: 10.3390/biom11020316.
The type III secretion system (T3SS) is a virulence apparatus used by many Gram-negative pathogenic bacteria to cause infections. Pathogens utilizing a T3SS are responsible for millions of infections yearly. Since many T3SS knockout strains are incapable of causing systemic infection, the T3SS has emerged as an attractive anti-virulence target for therapeutic design. The T3SS is a multiprotein molecular syringe that enables pathogens to inject effector proteins into host cells. These effectors modify host cell mechanisms in a variety of ways beneficial to the pathogen. Due to the T3SS's complex nature, there are numerous ways in which it can be targeted. This review will be focused on the direct targeting of components of the T3SS, including the needle, translocon, basal body, sorting platform, and effector proteins. Inhibitors will be considered a direct inhibitor if they have a binding partner that is a T3SS component, regardless of the inhibitory effect being structural or functional.
III 型分泌系统（T3SS）是许多革兰氏阴性致病菌用于引起感染的毒力装置。每年有数以百万计的感染是由利用 T3SS 的病原体引起的。由于许多 T3SS 敲除株无法引起全身感染，因此 T3SS 已成为治疗设计中一个有吸引力的抗毒力靶标。T3SS 是一种多蛋白分子注射器，使病原体能够将效应蛋白注入宿主细胞。这些效应子以多种方式修饰宿主细胞机制，有利于病原体。由于 T3SS 的复杂性质，有许多方法可以对其进行靶向。本综述将重点介绍 T3SS 组件的直接靶向，包括针、转位器、基底体、分拣平台和效应蛋白。如果抑制剂的结合伙伴是 T3SS 组件，无论其抑制作用是结构还是功能，都将被视为直接抑制剂。
