CHLAMYDIA TRACHOMATIS INCA MUTANTS

描述（改编自申请人的摘要）：C.沙眼变异体 不能在细胞中进行包涵体融合 文化这些变异株占西雅图临床分离株的1-2 并被定义为缺乏可检测的印加，这是一种衣原体蛋白， 定位于包涵体膜。26个独立的印加突变体 分离物已经被测序并被分成几个不同的类别。 拟议研究的总体目标是确定 野生型和非融合菌株，并利用定义的差异 以更好地了解衣原体的发展和发病机制。实验 计划研究分子和细胞生物学以及临床 变异衣原体的表现每种变体都将与 匹配的野生型对照。在第一个目标中，将进行分子分析， 确定印加表达缺失的机制， 其他Inc。第二个目标是非融合菌株的生长和发育 将在细胞培养模型中进行研究。最后，在第三个目标中， 非融合表型的相关性将使用 回顾性病例对照分析和衣原体感染的猴模型。 对这些自然突变体的研究将有助于更好地了解 衣原体的生长、发育和发病机制。

DESCRIPTION (Adapted from the Applicant's Abstract): C. trachomatis variants have been described that are incapable of undergoing inclusion fusion in cell culture. These variants represent 1-2 percent of clinical isolates in Seattle and have been defined as lacking detectable IncA, a chlamydial protein that localizes to the inclusion membrane. Twenty-six independent incA mutant isolates have been sequenced and organized into several distinct categories. The overall goal of the proposed research is to identify distinctions between wild type and non-fusogenic strains and to exploit differences that are defined to better understand chlamydial development and pathogenesis. Experiments are planned to examine molecular and cell biology as well as clinical manifestations of the mutant chlamydiae. Each variant will be compared with matched wild-type controls. In the first aim molecular analyses will be done to determine mechanisms responsible for loss of expression of IncA and possibly other Inc's. In the second aim, growth and development of non-fusogenic strains will be studied in cell culture models. Finally, in the third aim the clinical relevance of the non-fusogenic phenotype will be determined using a retrospective case-control analysis and a monkey model of chlamydial infection. Study of these natural mutants will lead to a better understanding of chlamydial growth, development and pathogenesis.