Chlamydial Pathogeneis in the Reproductive Tract

本项目(2)的目标是确定人类衣原体感染的基本相关因素。 在人类生殖道中繁殖五个区域。这将启动有效的翻译研究，通过 与疫苗开发和疫苗相关的衣原体的鉴定和特征 在雌性复杂的自然环境中起作用的生理或致病机制 并为可能的化疗干预提供靶点。这项工程涉及广泛的 与《儿童权利公约》的补充项目1和3合作，并将依靠核心B、C和D 分别提供豚鼠和人的血清和拭子，并对结果进行生物统计学分析。 在第一阶段，沙眼衣原体和卡瓦衣原体生殖器分离株的毒力将在重新鉴定中量化。 使用代表生殖器的Pfient队列来确定基因组序列类型和生殖道生态 人类中的衣原体疾病。毒力将通过基因组倍增、感染性产量、 包涵体融合性和病理学作为可测量的生理/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。 研究的第二阶段将是调查与基因组序列类型和 沙眼衣原体和豚鼠衣原体两个基因家族的功能多样性 编码毒力相关的III型包涵膜蛋白(INC)和效应蛋白 分泌(T3s)系统，可能是化疗干预的靶点。发展中的 选定的INC和T3S效应基因在沙眼衣原体和卡瓦衣原体的变种中的表达将是 将确定变异的Inc和T3S效应蛋白的特征和亚细胞和分子靶点。 疫苗靶向PMP基因家族和PMP特异性抗体应答的多样性。 /rac/7omaf/S感染患者和卡瓦线虫感染的豚鼠将被调查与 基因组序列类型与繁殖五区生态学。这将通过对 PMP基因在沙眼衣原体和卡氏衣原体变异株中的发育表达 在选定的变异体中PMP表达的频率开/关切换和执行横截面AND PMP特异性抗体应答在感染人群中的纵向比较研究 豚鼠。

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.