Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
Cell Microbiol. 2012 Oct;14(10):1554-67. doi: 10.1111/j.1462-5822.2012.01820.x. Epub 2012 Jun 19.
Chlamydia trachomatis is an obligate intracellular bacteria and the infectious agent responsible for the sexually transmitted disease Chlamydia. Infection with Chlamydia can lead to serious health sequelae such as pelvic inflammatory disease and reproductive tract scarring contributing to infertility and ectopic pregnancies. Additionally, chlamydial infections have been epidemiologically linked to cervical cancer in patients with a prior human papilomavirus (HPV) infection. Chlamydial infection of cultured cells causes multinucleation, a potential pathway for chromosomal instability. Two mechanisms that are known to initiate multinucleation are cell fusion and cytokinesis failure. This study demonstrates that multinucleation of the host cell by Chlamydia is entirely due to cytokinesis failure. Moreover, cytokinesis failure is due in part to the chlamydial effector CPAF acting as an anaphase promoting complex mimic causing cells to exit mitosis with unaligned and unattached chromosomes. These lagging and missegregated chromosomes inhibit cytokinesis by blocking abscission, the final stage of cytokinesis.
沙眼衣原体是一种专性细胞内细菌,也是引起性传播疾病沙眼衣原体的病原体。沙眼衣原体感染可导致严重的健康后遗症,如盆腔炎和生殖道瘢痕形成,导致不孕和宫外孕。此外,衣原体感染与 HPV 感染患者的宫颈癌在流行病学上有关联。培养细胞中的衣原体感染会导致多核化,这是染色体不稳定性的一种潜在途径。已知有两种机制可以引发多核化,即细胞融合和胞质分裂失败。本研究表明,衣原体引起宿主细胞的多核化完全是由于胞质分裂失败。此外,胞质分裂失败部分归因于衣原体效应因子 CPAF 作为后期促进复合物模拟物的作用,导致细胞在染色体未对齐和未附着的情况下退出有丝分裂。这些滞后和错误分离的染色体通过阻止胞质分裂的最后阶段——分裂后期的完成来抑制胞质分裂。