An infection with Chlamydia trachomatis causes one of the most frequently occurring sexually transmitted diseases worldwide. It can lead to pelvic inflammatory disease, ectopic pregnancy and infertility in the female genital tract. Doxycycline or azithromycin are current first choice treatment, even though up to 12.8% treatment failure has been reported for azithromycin recently. Hence, there is an urgent need for new substances fighting the infection. Sorangicin A blocks the bacterial DNA-dependent RNA-polymerase and therefore may become an important player in antibiotic research. In our working group we could already show that the substance is highly efficient against Chlamydia trachomatis infections in cell culture (unpublished data), indicating that it may also eradicate chlamydial infections in vivo.
Our aim is to establish a novel treatment strategy with Sorangicin A against chlamydial infections. We want to test the component in a mouse and human fallopian tube model in order to further investigate the effects on living organisms and human tissue.
For in vivo investigations, C57BL/6J female mice will be infected with Chlamydia muridarum. Sorangicin A will then be applicated systematically or topically. Evaluating the bacterial shedding and possible side effects, vaginal swabs and stool samples will be taken three days and then once a week after infection. Vaginal swab medium will be put on recovery plates to measure recoverable chlamydial inclusions. Microbiota analysis will be performed of the stool and vaginal samples to detect possible side effects of the antibiotic on the host´s microbioal composition. All mice will be sacrificed 43 days postinfection to investigate the gross pathologies of the urogenital tract. Pharmacokinetic analyses of serum as well as genital tissue will be performed. For ex vivo studies, human fallopian tubes will be infected with Chlamydia trachomatis, treated with Sorangicin A and put in to the incubator for 48 hours. Then, the material will be shredded in medium, which will also be put on recovery plates and incubated in order to calculate the recoverable inclusion forming units of Chlamydia trachomatis.