Mechanisms of temporal gene regulation in Chlamydia

描述（由申请人提供）：衣原体是一种对公众健康有重大影响的致病菌。2006年，美国疾病控制与预防中心报告了100多万例衣原体感染，使其成为最常见的传染病。这种生物引起疾病的能力与其在人类细胞内发生的不寻常的发育周期有关。我们的长期目标是了解这种病原体在发育周期中如何控制其基因的表达，从而使其能够生长和复制。我们的中心假设是，三个时间类别的早期，中期和晚期衣原体基因在转录水平上通过不同的机制协调调节。目的1将确定在中期测量的较高水平的衣原体DNA超卷曲是否被用作上调中期基因的一般机制。目的2将研究早期基因是否在感染开始时选择性表达，因为它们对阻止后期时间类基因转录的抑制剂具有抗性。目的3将研究两种抑制晚期基因以防止其过早表达的调节因子。这些研究的成功完成将有助于我们了解衣原体如何控制其基因的程序化表达。这些发现可能会导致通过中断发育周期来治疗衣原体感染的新治疗策略。

DESCRIPTION (provided by applicant): Chlamydia is a pathogenic bacterium with a significant impact on public health. In 2006, more than a million chlamydial infections were reported to the CDC making it the most commonly reported infectious disease. The ability of this organism to cause disease is related to its unusual developmental cycle, which takes place inside a human cell. Our long-term objective is to understand how this pathogen controls the expression of its genes during the developmental cycle so that it can grow and replicate. Our central hypothesis is that the three temporal classes of early, mid and late chlamydial genes are coordinately regulated at the transcriptional level by distinct mechanisms. Aim 1 will determine if the higher levels of chlamydial DNA supercoiling measured in midcycle are used as a general mechanism to upregulate mid genes. Aim 2 will investigate if early genes are selectively expressed at the start of the infection because they are resistant to an inhibitor that prevents transcription of later temporal classes of genes. Aim 3 will examine two regulators that repress late genes to prevent their premature expression. Successful completion of these studies will help us to understand how Chlamydia controls the programmed expression of its genes. These findings may lead to novel therapeutic strategies for treating chlamydial infections by interrupting the developmental cycle.