Inhibition of fungal pathogenicity by targeting the H <sub>2</sub> S-synthesizing enzyme cystathionine β-synthase
Wenqiang Chang, Ming Zhang, Xueyang Jin, Haijuan Zhang, Hongbo Zheng, Sha Zheng, Yanan Qiao, Haina Yu, Bin Sun, Xuben Hou, Hong‐Xiang Lou
Abstract
The global emergence of antifungal resistance threatens the limited arsenal of available treatments and emphasizes the urgent need for alternative antifungal agents. Targeting fungal pathogenic functions is an appealing alternative therapeutic strategy. Here, we show that cystathionine β-synthase (CBS), compared with cystathionine γ-lyase, is the major enzyme that synthesizes hydrogen sulfide in the pathogenic fungus Candida albicans . Deletion of CBS leads to deficiencies in resistance to oxidative stress, retarded cell growth, defective hyphal growth, and increased β-glucan exposure, which, together, reduce the pathogenicity of C. albicans . By high-throughput screening, we identified protolichesterinic acid, a natural molecule obtained from a lichen, as an inhibitor of CBS that neutralizes the virulence of C. albicans and exhibits therapeutic efficacy in a murine candidiasis model. These findings support the application of CBS as a potential therapeutic target to fight fungal infections.