Evaluation of the antifungal activity of microbial chondroitinsulfate on different candida strains in an experimentalvulvovaginal Candidiasis rat model

Chondroitin sulfate (CS) is a sulphated glycosaminoglycan with structural and signaling functions in the body. It is also widely used as a dietary supplement and active pharmaceutical agent worldwide. CS has been shown to contribute to bone mineralization, nerve development and angiogenesis, as well as to exhibit antioxidant and anti-inflammatory properties. Candida species cause a wide range of infections, from superficial and mucosal infections to invasive candidemia and metastatic organ involvement and are a major cause of morbidity and mortality in humans. Vulvovaginal candidiasis is a common vaginal infection affecting 70-75% of women at least once in their lifetime. There are still significant knowledge gaps regarding alternative antifungal treatment options for Candida infections. In this thesis, the antifungal activity of microbial CS (MCS) produced by biotechnological methods from the recombinant E. coli strain (C2987) was investigated in an experimental vulvovaginal candidiasis rat model against different Candida strains and compared with other commonly used antifungal agents. MCS was produced by transforming E. coli with the pETM6- PACF-vgb plasmid containing the kfoA, kfoC and kfoF genes involved in chondroitin synthesis as well as the Vitreoscilla hemoglobin gene (vgb). The structural integrity and purity of the product was confirmed by NMR and HPLC analyzes. In addition, the chemical composition of the cream formulations containing different concentrations of MCS was verified by FT-IR analyzes. In the experimental model of vulvovaginal candidiasis model, treatment groups, especially those treated with 0.5% and 1% MCS, showed statistically significant reductions in vaginal lavage fluid Candida colony counts and cytokine levels compared to the infected control group and those treated with known antifungal agents such as nystatin and fenticonazole. The efficacy of MCS, even at low doses, supports its potential protective and therapeutic effect against vaginal infections. These results emphasize the need for further investigation of MCS in clinical practice and its potential for wider use. Keywords: Antifungal activity, Candida spp., Microbial Chondroitin Sulfate, Vaginal candidiasis