Transcriptional Control of Chlamydial Development

描述(申请人提供)：沙眼衣原体是发展中国家可预防失明的主要原因，也是全世界报告的最常见的性传播感染。肺炎衣原体是全世界约10%的社区获得性呼吸道感染的原因。沙眼衣原体和肺炎衣原体与更严重的疾病后遗症有关，这些后遗症被认为是由于与持续性感染相关的慢性炎症条件而产生的。细胞因子干扰素？在控制衣原体感染方面发挥核心作用，并已被证明在细胞培养模型中诱导持续生长状态。在干扰素存在的情况下持续生长？已被证明可以阻断生物体的正常发育周期，并防止有机体分化为具有感染性的形式。我们计划研究非编码RNA家族在发育周期中的作用，以及与干扰素？诱导的持续生长相关的变化。需要检验的假设是，ncRNAs在发育周期中发挥重要作用，并在干扰素-β存在的情况下参与与持续生长相关的变化。非编码RNA将使用基因间和全基因组平铺微阵列进行识别，并将通过Northern分析和转录图谱程序进行确认。确认的非编码RNA的作用机制将通过在大肠杆菌中的共表达研究来研究。最后，将使用微阵列分析、定量基因表达分析以及基因表达和蛋白质表达相结合的研究来测试非编码RNA在沙眼衣原体和肺炎衣原体正常和干扰素诱导的持续生长过程中的调节作用。这项拟议的工作将使人们更全面地了解沙眼衣原体和肺炎衣原体的发育周期，并从机制上理解衣原体对人类先天免疫反应的反应。在一个快速发展的研究领域，调节性RNA代表了一类新的非传统抗菌药的靶点。 简介：致病性衣原体可导致呼吸道疾病、性传播疾病、致盲沙眼和相关的慢性病。该项目使用基因组水平分析来确定一类新的RNA调节器在正常生长和细菌对宿主免疫系统的反应中的作用。这些调节器控制细菌对环境反应的重要方面，它们在正常和慢性感染中的作用将被研究。

DESCRIPTION (provided by applicant): Chlamydia trachomatis is the leading cause of preventable blindness in developing countries and the most commonly reported sexually transmitted infection worldwide. Chlamydia pneumoniae is the cause of approximately 10% of community-acquired respiratory infections worldwide. C. trachomatis and C. pneumoniae have been implicated in more serious disease sequelae that have been proposed to arise due to chronic inflammatory conditions associated with persistent infections. The cytokine IFN-? plays a central role in controlling chlamydial infections and has been shown to induce a persistent growth state in cell culture models. Persistent growth in the presence of IFN-? has been shown to block the normal developmental cycle of the organisms and prevent the differentiation of the organism to the infectious form. We plan to study the role of a family of non-coding RNAs in the developmental cycle and the changes associated with IFN- ?- induced persistent growth. The hypothesis to be tested is that ncRNAs play an important role in the developmental cycle and are centrally involved in the changes associated with persistent growth in the presence of IFN-?. Non-coding RNAs will be identified using intergenic and genome-wide tiling microarrays and will be confirmed by Northern analysis and transcript mapping procedures. The mechanism of action of the confirmed non-coding RNAs will be studied using co-expression studies in Escherichia coli. Finally, the regulatory roles of non-coding RNAs will be tested during normal and IFN-?-induced persistent growth of C. trachomatis and C. pneumoniae using microarray analysis, quantitative gene expression analysis and combined gene expression and protein expression studies. The proposed work will result in a more complete understanding of the developmental cycle of C. trachomatis and C. pneumoniae and will lead to a mechanistic understanding of the chlamydial response to the human innate immune-response. Regulatory RNAs represent a new class of targets for non-traditional antibacterials in a rapidly developing field of study. Narrative: The pathogenic chlamydiae are responsible for respiratory disease, sexually transmitted disease, blinding trachoma and associated chronic diseases. This project uses genome level analyses to determine the role of a new class of RNA regulators in normal growth and the response of the bacteria to the host's immune system. These regulators control important aspects of the bacteria's response to its environment and their role in normal and chronic forms of infection will be studied.