Chlamydial Pathogeneis in the Reproductive Tract

生殖道中的衣原体致病菌

• 批准号: 7762440
• 负责人: PATRIK M BAVOIL
• 金额: $ 33.68万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-21 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762440
• 关键词: Address; Antibody Formation; Cavia; Cell Death; Cell Line; Cells; Cervical; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Collaborations; Complex; Cytosol; Development; Ecology; Environment; Epithelial Cells; Female; Frequencies; Gene Family; Genes; Genital system; Genomics; Germ-Free; Health; Human; Immune; In Vitro; Infection; Infertility; Inflammatory Response; Intervention; Investigation; Knowledge; Laboratories; Laboratory Study; Measurable; Measures; Membrane; Membrane Proteins; Methods; Microbe; Modeling; Molecular Target; Mus; Pathogenesis; Pathology; Patients; Pelvic Inflammatory Disease; Phase; Physiological; Play; Process; Property; Proteins; Reproductive Tract Infections; Research; Risk; Role; Serum; Swab; System; Therapeutic; Translational Research; Type III Secretion System Pathway; Vaccines; Vagina; Variant; Virulence; Virulence Factors; Woman; cohort; design; genome sequencing; member; pathogen; reproductive; response; trafficking; trait; vaccine development; ward

The objective of this project (2) is to characterize essential correlates of chlamydial infection of the human reproducfive tract jn the human reproductive tract. This will prime effective translational research through the identificafion and characterizafion of chlamydial anfigens of relevance to vaccine development and of physiologic or pathogenefic mechanisms that are at play in the complex, natural environment of the female genital tract and provide targets for possible chemotherapeutic intervenfion. The project involves extensive collaboration with the complementary projects 1 and 3 of the CRC and will rely on Cores B, C and D for the provision of guinea pig and human sera and swabs, and biostafistical analysis of the results, respectively. In a first phase, the virulence of C. trachomatis and C. cawae genital isolates will be quantified in relafionship to genome sequence type and reproductive tract ecology using a pafient cohort representative of genital chlamydial disease in humans. Virulence will be measured using genomic doubling, infecfious yield, inclusion fusogenicity and pathology as measurable physiological/pathogenic traits or endpoints, and using biomathemafical modeling of Intracellular development and correlated pathology. A second phase of the research will be to investigate in relationship to genome sequence type and reproducfive tract ecology the funcfional diversity of two gene families of C. trachomatis and C. caviae encoding inclusion membrane proteins (Inc) and effector proteins of the virulence-associated type III secretion (T3S) system that are targets for possible chemotherapeutic intervention. The developmental expression of selected inc and T3S effector genes in variants of C. trachomatis and C. cawae will be characterized and subcellular and molecular targets of variant Inc and T3S effector proteins will be identified. Finally, the diversity of the vaccine target pmp gene family and Pmp-specific antibody responses in C. /rac/7omaf/s-infected patients and C. cawae-infected guinea pigs will be investigated in relationship to genome sequence type and reproducfive tract ecology. This will be achieved through characterization of the developmental expression of pmp genes in variants of C. trachomatis and C. cawae, profiling the high frequency on/off switching of Pmp expression in selected variants and performing cross-sectional and longitudinal invesfigafions of the Pmp-specific anfibody response comparatively in infected humans and guinea pigs.

该项目 (2) 的目标是确定人类衣原体感染的基本相关性 生殖道 在人类生殖道中。这将通过以下方式启动有效的转化研究： 与疫苗开发相关的衣原体抗原的鉴定和表征 在女性复杂的自然环境中发挥作用的生理或致病机制 生殖道并为可能的化疗干预提供目标。该项目涉及广泛 与 CRC 的补充项目 1 和 3 合作，并将依靠核心 B、C 和 D 来实现 分别提供豚鼠和人类血清和拭子，并对结果进行生物统计分析。 在第一阶段，沙眼衣原体和卡瓦衣原体生殖分离株的毒力将在关系中进行量化 使用代表生殖器的患者队列来研究基因组序列类型和生殖道生态学 人类衣原体疾病。将使用基因组加倍、感染产量、 将融合性和病理学纳入可测量的生理/致病性状或终点，并使用 细胞内发育和相关病理学的生物数学模型。 研究的第二阶段将调查基因组序列类型和 生殖道生态学沙眼衣原体和豚鼠衣原体两个基因家族的功能多样性 编码毒力相关 III 型包涵膜蛋白 (Inc) 和效应蛋白 分泌（T3S）系统是可能的化疗干预的目标。发展性的 选定的 inc 和 T3S 效应基因在沙眼衣原体和卡瓦衣原体变种中的表达将 将鉴定变体 Inc 和 T3S 效应蛋白的特征、亚细胞和分子靶点。 最后，疫苗针对的 pmp 基因家族的多样性和 C. /rac/7omaf/s 感染的患者和 C. cawae 感染的豚鼠将被调查与 基因组序列类型和生殖道生态学。这将通过表征来实现 pmp 基因在沙眼衣原体和卡瓦衣原体变种中的发育表达，分析了高 选定变体中 Pmp 表达的频率开/关切换，并进行横截面和 对受感染人群和人群中 Pmp 特异性抗体反应的纵向研究 豚鼠。