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).
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