Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
Traffic. 2011 Jul;12(7):854-66. doi: 10.1111/j.1600-0854.2011.01204.x. Epub 2011 May 12.
Chlamydiae are Gram negative, obligate intracellular bacteria, and Chlamydia trachomatis is the etiologic agent of the most commonly reported sexually transmitted disease in the United States. Chlamydiae undergo a biphasic life cycle that takes place inside a parasitophorous vacuole termed an inclusion. Chlamydial infections have been epidemiologically linked to cervical cancer in patients previously infected by human papillomavirus (HPV). The inclusion associates very closely with host cell centrosomes, and this association is dependent upon the host motor protein dynein. We have previously reported that this interaction induces supernumerary centrosomes in infected cells, leading to multipolar mitotic spindles and inhibiting accurate chromosome segregation. Our findings demonstrate that chlamydial infection causes mitotic spindle defects independently of its effects on centrosome amplification. We show that chlamydial infection increases centrosome spread and inhibits the spindle assembly checkpoint delay to disrupt centrosome clustering. These data suggest that chlamydial infection exacerbates the consequences of centrosome amplification by inhibiting the cells' ability to suppress the effects of these defects on mitotic spindle organization. We hypothesize that these combined effects on mitotic spindle architecture identifies a possible mechanism for Chlamydia as a cofactor in cervical cancer formation.
衣原体是革兰氏阴性、专性细胞内细菌，沙眼衣原体是美国最常见的性传播疾病的病原体。衣原体经历一个双相生命周期，发生在一个称为包含体的寄生空泡内。衣原体感染与先前感染人乳头瘤病毒（HPV）的患者的宫颈癌在流行病学上有关。包含体与宿主细胞中心体密切相关，这种关联依赖于宿主的动力蛋白驱动蛋白。我们之前曾报道，这种相互作用在感染细胞中诱导额外的中心体，导致多极有丝分裂纺锤体，并抑制染色体的准确分离。我们的研究结果表明，衣原体感染会导致有丝分裂纺锤体缺陷，而不依赖于其对中心体扩增的影响。我们表明，衣原体感染增加了中心体的扩散，并抑制了纺锤体组装检查点的延迟，从而破坏了中心体的聚类。这些数据表明，衣原体感染通过抑制细胞抑制这些缺陷对有丝分裂纺锤体组织的影响的能力，加剧了中心体扩增的后果。我们假设，这些对有丝分裂纺锤体结构的综合影响确定了衣原体作为宫颈癌形成的协同因子的一种可能机制。
