Brown Heather M, Knowlton Andrea E, Snavely Emily, Nguyen Bidong D, Richards Theresa S, Grieshaber Scott S
Department of Oral Biology, University of Florida, Gainesville, Florida, United States of America.
Department of Molecular Genetics and Microbiology, Center for Microbial Pathogenesis, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS One. 2014 Jun 23;9(6):e100763. doi: 10.1371/journal.pone.0100763. eCollection 2014.
Chlamydia trachomatis is an obligate intracellular bacterial pathogen and the second leading cause of sexually transmitted infections in the US. Infections cause significant morbidity and can lead to serious reproductive sequelae, including an epidemiological link to increased rates of reproductive cancers. One of the overt changes that infected cells exhibit is the development of genomic instability leading to multinucleation. Here we demonstrate that the induction of multinucleation is not conserved equally across chlamydial species; C. trachomatis L2 caused high levels of multinucleation, C. muridarum intermediate levels, and C. caviae had very modest effects on multinucleation. Our data show that at least two effector pathways together cause genomic instability during infection leading to multinucleation. We find that the highly conserved chlamydial protease CPAF is a key effector for one of these pathways. CPAF secretion is required for the loss of centrosome duplication regulation as well as inducing early mitotic exit. The second effector pathway involves the induction of centrosome position errors. This function is not conserved in three chlamydial species tested. Together these two pathways contribute to the induction of high levels of genomic instability and multinucleation seen in C. trachomatis infections.
沙眼衣原体是一种专性细胞内细菌病原体，是美国性传播感染的第二大主要病因。感染会导致严重发病，并可能引发严重的生殖后遗症，包括与生殖癌症发病率上升存在流行病学关联。受感染细胞表现出的一个明显变化是基因组不稳定导致多核化。在此我们证明，多核化的诱导在衣原体物种中并非同等保守；沙眼衣原体L2导致高水平的多核化，鼠衣原体导致中等水平的多核化，豚鼠衣原体对多核化的影响非常小。我们的数据表明，至少两条效应途径共同导致感染期间的基因组不稳定，进而导致多核化。我们发现，高度保守的衣原体蛋白酶CPAF是其中一条途径的关键效应物。CPAF的分泌是中心体复制调控丧失以及诱导早期有丝分裂退出所必需的。第二条效应途径涉及中心体位置错误的诱导。在测试的三种衣原体物种中，该功能并不保守。这两条途径共同导致了沙眼衣原体感染中所见的高水平基因组不稳定和多核化。
