Abstract
Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM
Objectives
Candida albicans is a pathogenic yeast that causes candidiasis in immunocompromised patients. The overuse of antifungal drugs has led to the development of resistance to such drugs by this fungus, which is a major challenge in antifungal chemotherapy. The utilization of natural products is a significant trial for the development of new antifungals. Curcumin, one such natural product, has been widely studied as a drug candidate and is reported to exhibit antifungal activity against C. albicans. Although studies of the mechanism of curcumin against human cancer cells have shown that it inhibits heat shock protein 90 (Hsp90), little is known about its molecular function against C. albicans. In this work, we investigated the relationship between curcumin and Hsp90 of C. albicans.
Methods
For the molecular genetical analyses of C. albicans Hsp90, a doxycycline-mediated HSP90 strain and a HSP90-overexpressing strain of this fungus were constructed. The effect of curcumin on the gene expression of HSF1, AHR1, HOG1, and CDR1 as well as HSP90 was analyzed. Moreover, the stress responses to high temperature and osmotic pressure and the drug efflux of these strains were investigated.
Results
Curcumin reduced the transcription of HSP90 at the post-transcriptional level and it was suggested to lead to the decrease in Hsp90. This phenomenon resulted in the downregulation of HOG1 and CDR1. In addition, we confirmed curcumin also inhibited Cdr1 efflux activity in C. albicans.
Conclusion
Curcumin was suggested to influence not only HSP90 expression but also Cdr1 activity in C. albicans.