Transcriptional Control of Chlamydial Development

描述（由申请人提供）：沙眼衣原体是发展中国家可预防性失明的主要原因，也是全球最常见的性传播感染。肺炎衣原体是全球约10%的社区获得性呼吸道感染的原因。C. trachomatis和C.肺炎与更严重的疾病后遗症有关，所述疾病后遗症被认为是由于与持续感染相关的慢性炎性病症而引起的。细胞因子IFN-？在控制衣原体感染中起核心作用，并已显示在细胞培养模型中诱导持续生长状态。持续增长的IFN-？已显示阻断生物体的正常发育周期并阻止生物体分化为感染性形式。我们计划研究一个非编码RNA家族在发育周期中的作用以及与IFN-γ相关的变化。诱导持续增长。待检验的假设是，ncRNA在发育周期中发挥重要作用，并主要参与IFN-？存在下与持续生长相关的变化。将使用基因间和全基因组平铺微阵列鉴定非编码RNA，并通过北方分析和转录物作图程序进行确认。将使用大肠杆菌中的共表达研究来研究确认的非编码RNA的作用机制。最后，非编码RNA的调节作用将在正常和IFN-γ-IFN-γ诱导C. trachomatis和C.使用微阵列分析、定量基因表达分析以及组合的基因表达和蛋白质表达研究来分析肺炎链球菌。这项工作将使我们对C. trachomatis和C.并将导致衣原体对人类先天免疫应答的机制性理解。在快速发展的研究领域中，调控RNA代表了一类新的非传统抗菌药物的靶标。 叙述：病原性衣原体引起呼吸道疾病、性传播疾病、致盲性沙眼和相关慢性疾病。该项目使用基因组水平分析来确定一类新的RNA调节剂在正常生长和细菌对宿主免疫系统的反应中的作用。这些调节剂控制细菌对其环境的反应的重要方面，并且将研究它们在正常和慢性感染形式中的作用。

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.