EFFICACY OF MICROBICIDES IN CHLAMYDIA TRACHOMATIS

杀菌剂对沙眼衣原体的功效

• 批准号: 6233362
• 负责人: Priscilla B. Wyrick
• 金额: $ 5.82万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6233362
• 关键词: Alphaherpesvirinae; Chlamydia trachomatis; HeLa cells; antibacterial agents; cell migration; disease /disorder model; drug screening /evaluation; hormone regulation /control mechanism; inflammation; microorganism disease chemotherapy; neutrophil; sexually transmitted diseases; swine; topical drug application

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).

众所周知，生殖道沙眼衣原体血清型D-K是美国流行性性传播疾病（STD）的原因，估计每年有400万例病例。衣原体疾病可能是潜伏性的，它们构成了重要的初级、二级和三级保健问题，妇女在其中承受着特殊的负担，因为它们增加了对生殖产生不利后果的风险。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病。我们之前的研究表明，在已经感染沙眼衣原体E血清型的人类上皮细胞中，杀微生物剂C31 G可以进入衣原体内含物，从而破坏衣原体;此外，内含物膜完整性的改变导致衣原体LPS的胞吐增加，但热休克蛋白60却没有。因此，在具体目标1中，我们设计了一个共培养模型系统，以确定是否有炎症反应细胞迁移（PMN）的衣原体感染的HeLa细胞暴露于C31 G的调制。我在赫尔希医学院的同事已经证明，烷基硫酸盐在杀死乳头瘤病毒方面非常有效，除了单纯疱疹病毒（HSV）和艾滋病毒。因此，在具体目标2中，我们将评估新的局部杀微生物剂候选物单独以及与C31 G和烷基硫酸盐组合对双重感染C.沙眼和HSV。最后，我们将使用衣原体感染的猪模型来确定在不同的激素状态（增殖和分泌）下，杀微生物剂对衣原体感染的干预是如何改变的。