Taylor Lacey D, Nelson David E
Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th Street, Hamilton, MT 59840, USA,
Subcell Biochem. 2014;80:255-69. doi: 10.1007/978-94-017-8881-6_13.
Chlamydiae are obligate intracellular bacterial parasites that infect a wide range of metazoan hosts. Some Chlamydia species are important causes of chronic inflammatory diseases of the ocular, genital and respiratory tracts in humans. Genes located in a variable region of chlamydial genomes termed the plasticity zone are known to be key determinants of pathogenic diversity. The plasticity zone protein CT153, present only in select species, contains a membrane attack complex/perforin (MACPF) domain, which may mediate chlamydial interactions with the host cell. CT153 is present throughout the C. trachomatis developmental cycle and is processed into polypeptides that interact with membranes differently than does the parent protein. Chlamydiae interact extensively with membranes from the time of invasion until they eventually exit host cells, so numerous roles for a MACPF protein in pathogenesis of these pathogens are conceivable. Here, we present an overview of what is known about CT153 and highlight potential roles of a MACPF family protein in a group of pathogens whose intracellular development is marked by a series of interactions with host cell membranes and organelles. Finally, we identify new strategies for identifying CT153 functions made feasible by the recent development of a basic toolset for genetic manipulation of chlamydiae.
衣原体是专性细胞内寄生菌,可感染多种后生动物宿主。某些衣原体物种是人类眼部、生殖道和呼吸道慢性炎症疾病的重要病因。位于衣原体基因组可变区域(称为可塑性区)的基因是致病多样性的关键决定因素。仅在特定物种中存在的可塑性区蛋白CT153含有膜攻击复合物/穿孔素(MACPF)结构域,该结构域可能介导衣原体与宿主细胞的相互作用。CT153在沙眼衣原体的整个发育周期中均有表达,并被加工成与母蛋白在与膜相互作用方式上不同的多肽。从入侵之时起,衣原体就与膜广泛相互作用,直至最终离开宿主细胞,因此可以想象MACPF蛋白在这些病原体的发病机制中具有多种作用。在此,我们概述了关于CT153的已知信息,并强调了MACPF家族蛋白在一类病原体发病机制中的潜在作用,这类病原体的细胞内发育以与宿主细胞膜和细胞器的一系列相互作用为特征。最后,我们确定了通过衣原体基因操作基础工具集的最新发展而可行的鉴定CT153功能的新策略。