A renewed tool kit to explore Chlamydia pathogenesis: from molecular genetics to new infection models.
A renewed tool kit to explore Chlamydia pathogenesis: from molecular genetics to new infection models.
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DOI：
10.12688/f1000research.18832.1
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Valdivia, Raphael H
中科院分区：
文献类型：
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作者：
Dolat, Lee;Valdivia, Raphael H
沙眼衣原体是最常见的性传播细菌病原体，也是发展中国家可预防失明的主要原因。沙眼衣原体侵入结膜和生殖道上皮，并在被称为包涵体的细胞膜内复制。为了在哺乳动物细胞中入侵和复制，衣原体通过重组细胞骨架和细胞-细胞黏附来重塑上皮表面，重新编程膜运输，并调节细胞信号以抑制先天免疫反应。如果感染上升到女性生殖道上部，就会导致盆腔炎和组织疤痕形成。沙眼衣原体感染与不孕症、宫外孕、子宫内膜异位症，以及潜在的子宫颈癌和子宫癌有关。不幸的是，由于缺乏研究衣原体的分子遗传学工具，以及体内和体外感染模型的局限性，这种临床上重要的人类病原体颠覆宿主细胞功能和导致疾病的分子机制仍然知之甚少。在这篇综述中，我们讨论了可用于解剖沙眼衣原体感染的实验分子工具箱的最新进展，特别关注衣原体通过调节上皮细胞-细胞连接的结构、功能和动力学来诱导上皮屏障的破坏。
Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen and the leading cause of preventable blindness in the developing world. C. trachomatis invades the epithelium of the conjunctiva and genital tract and replicates within an intracellular membrane-bound compartment termed the inclusion. To invade and replicate in mammalian cells, Chlamydia remodels epithelial surfaces by reorganizing the cytoskeleton and cell-cell adhesions, reprograms membrane trafficking, and modulates cell signaling to dampen innate immune responses. If the infection ascends to the upper female genital tract, it can result in pelvic inflammatory disease and tissue scarring. C. trachomatis infections are associated with infertility, ectopic pregnancies, the fibrotic disorder endometriosis, and potentially cancers of the cervix and uterus. Unfortunately, the molecular mechanisms by which this clinically important human pathogen subverts host cellular functions and causes disease have remained relatively poorly understood because of the dearth of molecular genetic tools to study Chlamydiae and limitations of both in vivo and in vitro infection models. In this review, we discuss recent advances in the experimental molecular tool kit available to dissect C. trachomatis infections with a special focus on Chlamydia-induced epithelial barrier disruption by regulating the structure, function, and dynamics of epithelial cell-cell junctions.