Genetic Regulation of Developmental Transitions in Chlamydia

摘要 WSU/UI-衣原体发育转变的遗传调控 衣原体属细菌包括重要的人类病原体沙眼衣原体，沙眼衣原体是引起 性传播感染和肺炎，肺炎是导致严重呼吸道疾病的原因之一。所有衣原体 是专性的细胞内寄生虫，依靠宿主细胞的感染经历两个阶段的发育 周而复始。在感染基本体(EB)侵入宿主细胞后，向复制型但非复制型转变 感染性网状小体(RB)是繁殖所必需的。将RB重新区分为EB是 对于产生传染性后代来说是必不可少的。EB形式历来被认为是代谢惰性的。 然而，最近的数据表明，EBS可以对特定的分子信号做出反应，包括葡萄糖6- 预测存在于粘膜表面的磷酸盐和三磷酸腺苷。EBS的应对能力 特定的营养素与它们对环境中的暗示做出积极反应的能力是一致的，甚至在 内化为宿主细胞。通过分析EB入侵前的分子事件(例如，转录和 随着时间的推移保持传染性)和数学建模，这个项目的目的是确定 与粘膜表面的初始相互作用中主动EB代谢反应的研究和基因的鉴定 控制衣原体形态分化的调节事件。

ABSTRACT WSU / UI - Genetic regulation of developmental transitions in Chlamydia Bacteria of the genus Chlamydia include the significant human pathogens C. trachomatis, a leading cause of sexually transmitted infections, and C. pneumonia, a cause of significant respiratory disease. All chlamydiae are obligate intracellular parasites that depend on infection of a host cell to undergo a bi-phasic developmental cycle. Following host cell invasion by the infectious Elementary Body (EB), transition to the replicative but non- infectious Reticulate Body (RB) is essential for propagation. Differentiation of the RB back to the EB is essential to generate infectious progeny. The EB form has historically been regarded as metabolically inert. However, recent data suggest that EBs can respond to specific molecular signals, including glucose 6- phosphate and ATP that are predicted to be present at mucosal surfaces. The ability of EBs to respond to specific nutrients is consistent with their ability to respond actively to cues in their environment even before internalization into a host cell. Via analysis of EB pre-invasion molecular events (e.g., transcription, and maintenance of infectivity over time) and mathematical modeling, this project is aimed at determining the role of active EB metabolic responses during initial interactions with mucosal surfaces, and identification of gene regulatory events that control chlamydial morphological differentiation.