Chlamydia trachomatis, Genital Flora, & STD Pathogenesis

沙眼衣原体、生殖器菌群、

基本信息

批准号：
6712806
负责人：
Gerald Irwin Byrne
金额：
$ 18.23万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-03-15 至 2006-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6712806
关键词：
Chlamydia trachomatis Lactobacillus communicable disease transmission disease /disorder model female genetic strain indoles laboratory mouse microorganism interaction microorganism metabolism pathologic process reproductive system infection sexually transmitted diseases tissue /cell culture tryptophan

项目摘要

DESCRIPTION (provided by applicant): Chlamydial genital tract infections in women continue to be a huge public health problem in the United States and across the globe. These infections also can become personal tragedies for infected individuals since they frequently lead to upper genital tract sequelae that can result in involuntary infertility due to tubal scarring and occlusion. C. trachomatis genital tract infections in women also occur in a polymicrobial environment, but little information is available on how the female genital flora affects disease outcome caused by Chlamydiae. Recent studies demonstrate that C. trachomatis genital isolates differ from ocular strains in that the former have functional tryptophan biosynthetic genes, whereas ocular strains do not. Chlamydial strains that have the capacity to produce tryptophan may be at a distinct advantage in the in vivo environment, since a major chlamydial antimicrobial effect elicited by host immune reactivity is manifest in chlamydial host cells through the induction of a tryptophan decylcizing enzyme (indoleamine 2,3-dioxygenase, [IDO]) after activation by the CD4+, Th1 effector cytokine, gamma interferon. The tryptophan operon in genital C. trachomatis isolates, however, is incomplete in that indole or indole derivatives are required for tryptophan production by these strains. Indole is produced neither by Chlamydiae nor the human host, and the hypothesis to be tested in this application is that normal indole-producing genital flora contribute to Chlamydiae disease pathogenesis by producing the substrate necessary for C. trachomatis to survive and grow in the lower genital tract and thereby contribute to improved transmission potential as well as the possibility for more severe upper genital tract consequences. This hypothesis will be tested by determining the effects of indole-producing normal flora on chlamydial genital tract disease in a well-characterized murine model.

描述（由申请人提供）：女性生殖道衣原体感染仍然是美国和全球的一个巨大的公共卫生问题。这些感染也可能成为感染者的个人悲剧，因为它们经常导致上生殖道后遗症，从而可能因输卵管疤痕和闭塞而导致非自愿不孕。女性沙眼衣原体生殖道感染也发生在多种微生物环境中，但关于女性生殖器菌群如何影响衣原体引起的疾病结果的信息很少。最近的研究表明，沙眼衣原体生殖分离株与眼部菌株不同，前者具有功能性色氨酸生物合成基因，而眼部菌株则没有。具有产生色氨酸能力的衣原体菌株在体内环境中可能具有明显的优势，因为宿主免疫反应性引起的主要衣原体抗菌作用通过诱导色氨酸脱环酶（吲哚胺2， 3-双加氧酶，[IDO]）被 CD4+、Th1 效应细胞因子、γ 干扰素激活后。然而，生殖器沙眼衣原体分离株中的色氨酸操纵子是不完整的，因为这些菌株产生色氨酸需要吲哚或吲哚衍生物。吲哚既不是由衣原体产生，也不是由人类宿主产生，本申请中要测试的假设是，正常产生吲哚的生殖器菌群通过产生沙眼衣原体在下生殖器中生存和生长所需的底物，从而促进衣原体疾病的发病机制。道，从而有助于提高传播潜力以及造成更严重的上生殖道后果的可能性。该假设将通过确定产生吲哚的正常菌群对特征明确的小鼠模型中衣原体生殖道疾病的影响来检验。