Department of Pathology and Microbiology, University of Nebraska Medical Center, Durham Research Center II, Omaha, Nebraska, USA.
Microbiol Mol Biol Rev. 2023 Sep 26;87(3):e0003423. doi: 10.1128/mmbr.00034-23. Epub 2023 Jun 26.
Type III secretion systems (T3SSs) are utilized by Gram-negative pathogens to enhance their pathogenesis. This secretion system is associated with the delivery of effectors through a needle-like structure from the bacterial cytosol directly into a target eukaryotic cell. These effector proteins then manipulate specific eukaryotic cell functions to benefit pathogen survival within the host. The obligate intracellular pathogens of the family have a highly evolutionarily conserved nonflagellar T3SS that is an absolute requirement for their survival and propagation within the host with about one-seventh of the genome dedicated to genes associated with the T3SS apparatus, chaperones, and effectors. Chlamydiae also have a unique biphasic developmental cycle where the organism alternates between an infectious elementary body (EB) and replicative reticulate body (RB). T3SS structures have been visualized on both EBs and RBs. And there are effector proteins that function at each stage of the chlamydial developmental cycle, including entry and egress. This review will discuss the history of the discovery of chlamydial T3SS and the biochemical characterization of components of the T3SS apparatus and associated chaperones in the absence of chlamydial genetic tools. These data will be contextualized into how the T3SS apparatus functions throughout the chlamydial developmental cycle and the utility of heterologous/surrogate models to study chlamydial T3SS. Finally, there will be a targeted discussion on the history of chlamydial effectors and recent advances in the field.
III 型分泌系统(T3SS)被革兰氏阴性病原体用于增强其发病机制。该分泌系统与通过细菌细胞质中的针状结构将效应物直接递送至靶真核细胞有关。这些效应蛋白随后操纵特定的真核细胞功能,有利于病原体在宿主内的存活。家族中的专性细胞内病原体具有高度进化保守的非鞭毛 T3SS,这是它们在宿主内生存和繁殖的绝对要求,大约有七分之一的基因组专门用于与 T3SS 装置、伴侣蛋白和效应蛋白相关的基因。衣原体也有一个独特的两相发育周期,其中生物体在感染性的原体(EB)和复制性的网状体(RB)之间交替。T3SS 结构已在 EB 和 RB 上可视化。并且有一些效应蛋白在衣原体发育周期的每个阶段发挥作用,包括进入和退出。本综述将讨论衣原体 T3SS 的发现历史以及在缺乏衣原体遗传工具的情况下 T3SS 装置和相关伴侣蛋白的生化特征。这些数据将被置于 T3SS 装置在整个衣原体发育周期中的功能以及异源/替代模型在研究衣原体 T3SS 中的用途的背景下进行讨论。最后,将有针对性地讨论衣原体效应蛋白的历史和该领域的最新进展。