EFFICACY OF MICROBICIDES IN CHLAMYDIA TRACHOMATIS

众所周知，生殖器沙眼衣原体D-K血清型是美国流行性传播疾病(STDS)的罪魁祸首，估计每年有400万例。衣原体疾病可能是潜伏的，它们构成了重大的初级、二级和三级保健问题，其中妇女承担着特别的负担，因为她们增加了不良生殖后果的风险。显然，迫切需要安全、有效、女性控制的局部杀微生物剂来帮助预防和控制性传播疾病。我们之前的研究表明，在已经感染沙眼衣原体血清E的人上皮细胞中，杀菌剂C31G可以接触到衣原体包涵体，从而对衣原体造成破坏；此外，包涵膜完整性的改变会导致衣原体内毒素的胞吐增加，但不会增加热休克蛋白60的排泄。因此，在特定的目标1中，我们设计了一个共培养模型系统，以确定C31G是否对衣原体感染的HeLa细胞的炎性反应细胞迁移(PMN)有调节作用。我在好时医学院的同事们已经证明，除了单纯疱疹病毒(HSV)和艾滋病毒外，烷基硫酸盐在杀死乳头状瘤病毒方面也非常有效。因此，在特定目标2中，我们将评估新的局部候选杀微生物剂单独以及与C31G和烷基硫酸盐联合使用对双重感染沙眼衣原体和单纯疱疹病毒的HeLa细胞的作用。最后，我们将使用衣原体感染的猪模型来确定或如何改变杀微生物剂对衣原体感染的干预在不同的激素状态(增殖和分泌)。

It is well recognized that genital Chlamydia trachomatis serovars D-K are responsible for epidemic sexually transmitted diseases (STDs) in the USA, with an estimated annual 4 million cases. Chlamydial diseases can be insidious and they constitute significant primary, secondary and tertiary health care concerns in which women bear a special burden because of their increased risk of adverse reproductive consequences. Clearly, safe, effective, female-controlled topical microbicides are urgently need to help prevent and control STDs. Our previous studies showed that in human epithelial cells already infected with C, trachomatis serovar E, the microbicide C31G gains access to the chlamydial inclusions causing destruction to chlamydiae; in addition, the alteration in inclusion membrane integrity results in increased exocytosis of chlamydial LPS but not heat shock protein 60. Thus, in Specific Aim 1, we have devised a co-culture model system to determine if there is modulation of inflammatory response cell migration (PMN) to chlamydiae-infected HeLa cells exposed to C31G. My colleagues at Hershey Medical School have shown that alkyl sulfates are quite effective in killing papillomavirus, in addition to herpes simplex (HSV) and HIV. So, in Specific Aim 2, we will evaluate the action of the new topical microbicide candidate alone and in combination with C31G and alkyl sulfates on HeLa cells doubly infected with C. trachomatis and HSV. Finally, we shall use a pig model of chlamydial infection to determine or how microbicide intervention of chlamydial infection is altered in the different hormonal states (proliferative and secretory).