Genetic Regulation of Developmental Transitions in Chlamydia

摘要 WSU / UI -衣原体发育转变的遗传调控 衣原体属的细菌包括重要的人类病原体C.沙眼是导致 性传播感染和C.肺炎，一种重要的呼吸道疾病的原因。所有衣原体 是专性细胞内寄生虫，其依赖于宿主细胞的感染来经历双相发育 周期在感染性基本体（EB）侵入宿主细胞后，向复制型但非复制型转化。 传染性网状体（RB）是繁殖所必需的。RB与EB的区别在于 对产生传染性后代至关重要。EB形式历来被认为是代谢惰性的。 然而，最近的数据表明，EB可以响应特定的分子信号，包括葡萄糖6- 磷酸盐和ATP，预计存在于粘膜表面。EB的反应能力 特定的营养物质与他们对环境中的线索做出积极反应的能力相一致， 内化到宿主细胞中。通过分析EB侵袭前的分子事件（例如，转录和 随着时间的推移保持传染性）和数学建模，该项目旨在确定 在与粘膜表面的初始相互作用过程中的活性EB代谢反应， 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.