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. One approach to this problem involves the utilization of new natural products as an alternative source of 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 function against C. albicans. In this paper, using a doxycycline-mediated HSP90 strain and an HSP90-overexpressing strain of C. albicans, we demonstrated that the curcumin triggered a decrease in Hsp90 by affecting it at the post-transcriptional level. This also led to the downregulation of HOG1 and CDR1, resulting in a reduction of the stress response and efflux pump activity of C. albicans. However, the inhibition of HSP90 by curcumin was not due to the inhibition of transcription factors HSF1 or AHR1. We also found that curcumin can not only decrease the transcriptional expression of CDR1, but also inhibit the efflux pump activity of Cdr1. Hence, we conclude that disruption of HSP90 by curcumin could impair cell growth, stress responses and efflux pump activity of C. albicans.

Summary Candida glabrata represents the second‐most frequent cause of candidiasis infections of the mucosa, bloodstream and genito‐urinary tract in immunocompromised individuals. The incidence of C glabrata infection has increased significantly in the last two decades, mainly due to this species’ abilities to resist various antifungal drugs and to form biofilms. We focused on the relationship between biofilm formation and the product of QDR2, a C glabrata member of the major facilitator superfamily (MFS) gene family, given that fungal biofilm formation limits drug penetration and is associated with persistent infection. The fungal cells in biofilms were compared between a C glabrata ∆qdr2 mutant and its wild‐type strain. Cells were analysed for metabolism activity and drug susceptibility (using tetrazolium assay), adhesion activity, growth assay and intracellular pH (using flow cytometry). Compared to the wild type, the C glabrata ∆qdr2 showed lower adhesion activity and higher fluconazole susceptibility when assessed as a biofilm. The mutant also showed decreased metabolic activity during biofilm formation. Furthermore, the mutant grew more slowly under neutral‐basic pH conditions. The qdr2 deletion in C glabrata resulted in an impaired ability to maintain pH homeostasis, which led in turn to a reduction of cell growth and of adherence to an artificial matrix. These results suggested that the Qdr2p function is needed for proper biofilm formation and biofilm maintenance in C glabrata as well as biofilm drug resistance towards fluconazole. Qdr2p may play an important role in C glabrata's ability to form biofilms on implanted medical devices in human bodies.

Candida glabrata is one of the commensal fungal species in human. In immune compromised individuals, it becomes one of the second major causes of candidiasis in mucosal, blood stream, and genito-urinary tract. high incidences of C. glabrata

Vph1 is associated with the copper homeostasis of Cryptococcus neoformans serotype D 1

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.