VIRULENCE FACTORS OF CHLAMYDIAE

沙眼衣原体血清型D-K是美国和世界范围内细菌获得性性传播疾病及其后遗症的最常见原因，包括前列腺炎、附睾炎、盆腔炎、异位妊娠和不育症。 衣原体疾病是潜伏性的，它们构成了重大的一级、二级和三级健康问题，妇女承受着特殊的负担，因为它们增加了对生殖产生不利后果的风险。 本实验室25年来的目标一直是试图了解衣原体在其宿主上皮细胞中生长的基本生物学，以了解感染过程，并允许解剖持续感染的细胞和分子后果，因为大多数衣原体输卵管疾病似乎是由慢性亚临床持续感染引起的。 这个建议是一个持续的努力，以了解关键的附着/进入步骤，在衣原体感染的上皮细胞中的信号，触发中性粒细胞趋化性-因为持久的衣原体抗原的炎症反应延长被认为是负责的损害和后遗症，和激素调节的进入和信号的中性粒细胞。 在目的1中，衣原体感染相关的hsp 70及其共伴侣蛋白GrpE和Dna J将与已知的和疑似的粘附素一起沿着掺入脂质体中，以确定hsp 70在进入中的作用，并且在目的2中，帮助鉴定与新鉴定的雌激素应答性受体辅助蛋白一起起作用的受体。 同样在目标2中，猪C。将开发沙眼衣原体S45分离株-猪生殖器组织感染模型，以剖析进入和中性粒细胞信号传导的激素调节（目的3）。 在目标3中，将比较触发中性粒细胞对极化HeLa细胞的趋化性的衣原体和趋化因子信号，所述极化HeLa细胞正常且持续地感染有非侵入性、无症状血清型E与侵入性、有症状血清型L2。 最后，在目标4中，冷冻电子显微镜和密度梯度将用于显示衣原体抗原分泌和运输可以通过从衣原体包涵体夹取的囊泡发生。

Chlamydia trachomatis serovars D-K are the most common cause, in the USA and worldwide, of bacterially-acquired sexually transmitted diseases and their sequelae, including prostatitis, epididymitis, pelvic inflammatory disease, ectopic pregnancy and sterility. Chlamydial diseases are insidious and they constitute significant primary, secondary and tertiary health concerns in which women bear a special burden because of their increased risk of adverse reproductive consequences. The goal of this laboratory for 25 years has been to try to understand the basic biology of chlamydial growth in its host epithelial cell in order to understand the infectious process and to permit dissection of the cellular and molecular consequences of persistent infection, since the majority of chlamydial tubal disease appears to result from chronic subclinical, persistent infection. This proposal is a continuation of on-going efforts to understand the crucial attachment/entry steps, the signals in chlamydiae-infected epithelial cells which trigger neutrophil chemotaxis--since a prolonged inflammatory response to persistent chlamydial antigens is believed to be responsible for the damage and sequelae, and hormone modulation of entry and signaling of neutrophils. In Aim 1, the chlamydial envelope-associated hsp70 and its co- chaperonins GrpE and DnaJ will be incorporated into liposomes, along with known and suspected adhesins, to define the role of hsp70 in entry and, in Aim 2, help identify the receptor which functions with newly identified, estrogen-responsive receptor accessory proteins. Also in Aim 2, the swine C. trachomatis S45 isolate- swine genital tissue model of infection will be developed to dissect hormone modulation of entry and neutrophil signaling (Aim 3). In Aim 3, a comparison will be made of chlamydial and chemokine signals triggering neutrophil chemotaxis to polarized HeLa cells normally and persistently infected with non-invasive, asymptomatic serovar E versus invasive, symptomatic serovar L2. Finally, in Aim 4, cryo-electron microscopy and density gradients will be used to show that chlamydial antigen secretion and trafficking can occur via vesicles pinched off from the chlamydial inclusion.