CHLAMYDIA AND THE PATHOGENESIS OF REITER'S SYNDROME

衣原体和 REITER 综合征的发病机制

• 批准号: 2081883
• 负责人: ALAN PAUL HUDSON
• 金额: $ 14.02万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2081883
• 关键词: Chlamydia trachomatis; Reiter's syndrome; antibiotics; bacterial DNA; bacterial RNA; bactericidal immunity; cytology; drug resistance; electron microscopy; in situ hybridization; molecular pathology; nucleic acid probes; pathologic process; polymerase chain reaction; ribosomal RNA; synovial fluid; virulence

An infectious etiology for Reiter's syndrome (RS) has long been suspected, since this disease has often been observed to follow episodes of urethritis or dysentery. Although many bacterial species can be associated with the disease, Chlamydia trachomatis has emerged as a primary etiologic agent in RS, due largely to its prevalence in the population. Although this organism is the major sexually-transmitted bacterium in the industrialized world, many aspects of the natural history of such infections remain relatively poorly understood; eg, both epidemiological and clinical features of chlamydial infections suggest that the organism can persist in a culture-negative state under some circumstances. Recent work from this laboratory has provided direct molecular biological evidence for persistent/inapparent chlamydial infections in all anatomically relevant sites; ie, we demonstrated that high levels of chlamydial nucleic acids can be demonstrated, via a simple molecular hybridization screening assay and by polymerase chain reaction (PCR)-based analysis, in conjunctival samples from trachoma patients and in standard urethral and cervical swabs, all of which are chlamydia- negative by standard culture or antibody-based screening assays. Importantly, we also demonstrated that culture-negative synovial tissues from RS patients similarly contain high levels of chlamydial RNA and DNA, while parallel samples from patients with other arthropathies do not. Further, preliminary evidence indicates that the nucleic acids shown in either hybridization or PCR assays are derived from viable, metabolically-active chlamydia. In this application, we describe studies to assess the prevalence and clinical consequences of inapparent chlamydial infection of the synovium in patients with/without RS. In these and related laboratory studies, we address clinical, biochemical, and molecular biological questions regarding the significance, natural history, characteristics, mechanisms of pathogenesis, and antibiotic susceptibility of such inapparent chlamydial infections. We further propose detailed molecular genetic studies to define the transcriptional and overall metabolic activity of inapparently-infecting chlamydial cells, and we describe experiments to investigate one possible mechanism for the reactivation of inapparent synovial chlamydial infection. These studies will give new insights for development of effective treatment programs for RS patients, and they will augment our understanding of an important but as yet poorly recognized facet of the chlamydial pathogenesis process.

赖特综合征（RS）的感染性病因长期以来一直是 怀疑，因为这种疾病经常被观察到， 尿道炎或痢疾 虽然许多细菌物种可以 与该病相关的沙眼衣原体已经成为一种 RS的主要病原体，主要是由于其在 人口 虽然这种生物是主要的性传播 细菌在工业化的世界，许多方面的自然 此类感染的历史仍然相对知之甚少;例如，两者 衣原体感染的流行病学和临床特征表明， 生物体可以在某些条件下保持阴性培养状态， 情节 该实验室最近的工作提供了直接的 持续性/隐性衣原体感染的分子生物学证据 所有解剖学相关部位的感染;即，我们证明， 高水平的衣原体核酸可以通过一个简单的 分子杂交筛选试验和聚合酶链反应 （PCR）为基础的分析，在结膜样本沙眼患者和 在标准的尿道和宫颈拭子中，所有这些都是衣原体- 通过标准培养或基于抗体的筛选测定为阴性。 重要的是，我们还证明了培养阴性的滑膜组织 来自RS患者的同样含有高水平的衣原体RNA和DNA， 而来自其他关节病患者的平行样品则没有。 此外，初步证据表明， 杂交或PCR测定源自活的， 代谢活跃的衣原体 在本申请中，我们描述了研究 评估隐性遗传的患病率和临床后果 有/无RS患者的滑膜衣原体感染。 在 这些和相关的实验室研究，我们解决临床，生化， 和分子生物学的问题， 历史、特点、发病机制和抗生素 这种隐性衣原体感染的易感性。 我们进一步 提出详细的分子遗传学研究，以确定转录 以及不明显感染衣原体的总体代谢活性 细胞，我们描述了实验，以调查一种可能的机制 不明显的滑膜衣原体感染的复发 这些 研究将为开发有效治疗提供新的见解 RS患者的计划，他们将增加我们对 衣原体的一个重要但尚未得到充分认识的方面， 发病过程