The trans-Golgi SNARE syntaxin 10 is required for optimal development of Chlamydia trachomatis.
The trans-Golgi SNARE syntaxin 10 is required for optimal development of Chlamydia trachomatis.
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DOI：
10.3389/fcimb.2015.00068
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发表时间：
2015
影响因子：
5.7
通讯作者：
Rucks EA
中科院分区：
文献类型：
--
作者：
Lucas AL;Ouellette SP;Kabeiseman EJ;Cichos KH;Rucks EA
沙眼衣原体是一种专性细胞内病原体，生长在称为包涵体的空泡内。在包涵体中，生物体从感染性的基本体（EB）分化为网状体（RB）。RB通过包涵体膜与宿主细胞沟通，以获得分裂所需的营养物质，从而扩大衣原体种群。在发育周期的后期，RB对未知的分子信号作出反应，重新分化为感染性EB，从而使感染周期持续下去。衣原体从宿主体内获取必需营养物质和代谢产物的一种策略是阻断宿主囊泡运输途径。在这项研究中，我们证明了一个trans-Golgi可溶性N-乙基马来酰亚胺敏感因子附着蛋白（SNARE），syntaxin 10，和/或syntaxin 10相关的高尔基体元素共定位与衣原体包涵体。我们假设衣原体利用包涵体膜上的突触融合蛋白10的分子机制来拦截特定的囊泡运输途径，以创造和维持最佳的包涵体内环境。为了验证这一假设，我们使用siRNA敲低syntaxin 10来研究syntaxin 10的缺失对衣原体生长和发育的影响。我们的研究结果表明，损失的syntaxin 10导致缺陷，在正常的衣原体成熟，包括：可变的夹杂物大小与更少的衣原体微生物每个夹杂物，更少的感染性后代，和延迟或停止RB-EB分化。衣原体发育中的这些缺陷与突触融合蛋白10敲低细胞中培养的包涵体保留的过量NBD-脂质相关。总的来说，在包涵体膜处的突触融合蛋白10的缺失对衣原体有负面影响。了解宿主机制参与维持最佳的包容环境，以支持衣原体的生长和发展是至关重要的了解分子信号参与成功的进展，通过衣原体发育周期。
Chlamydia trachomatis, an obligate intracellular pathogen, grows inside of a vacuole, termed the inclusion. Within the inclusion, the organisms differentiate from the infectious elementary body (EB) into the reticulate body (RB). The RB communicates with the host cell through the inclusion membrane to obtain the nutrients necessary to divide, thus expanding the chlamydial population. At late time points within the developmental cycle, the RBs respond to unknown molecular signals to redifferentiate into infectious EBs to perpetuate the infection cycle. One strategy for Chlamydia to obtain necessary nutrients and metabolites from the host is to intercept host vesicular trafficking pathways. In this study we demonstrate that a trans-Golgi soluble N-ethylmaleimide–sensitive factor attachment protein (SNARE), syntaxin 10, and/or syntaxin 10-associated Golgi elements colocalize with the chlamydial inclusion. We hypothesized that Chlamydia utilizes the molecular machinery of syntaxin 10 at the inclusion membrane to intercept specific vesicular trafficking pathways in order to create and maintain an optimal intra-inclusion environment. To test this hypothesis, we used siRNA knockdown of syntaxin 10 to examine the impact of the loss of syntaxin 10 on chlamydial growth and development. Our results demonstrate that loss of syntaxin 10 leads to defects in normal chlamydial maturation including: variable inclusion size with fewer chlamydial organisms per inclusion, fewer infectious progeny, and delayed or halted RB-EB differentiation. These defects in chlamydial development correlate with an overabundance of NBD-lipid retained by inclusions cultured in syntaxin 10 knockdown cells. Overall, loss of syntaxin 10 at the inclusion membrane negatively affects Chlamydia. Understanding host machinery involved in maintaining an optimal inclusion environment to support chlamydial growth and development is critical toward understanding the molecular signals involved in successful progression through the chlamydial developmental cycle.