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  3. Inhibition of fungal pathogenicity by targeting the H2S-synthesizing enzyme cystathionine β-synthase

Inhibition of fungal pathogenicity by targeting the H2S-synthesizing enzyme cystathionine β-synthase

  • Sci Adv. 2022 Dec 16;8(50):eadd5366. doi: 10.1126/sciadv.add5366.
Wenqiang Chang 1,  Ming Zhang 2,  Xueyang Jin 1,  Haijuan Zhang 3,  Hongbo Zheng 1,  Sha Zheng 1 4,  Yanan Qiao 1,  Haina Yu 1,  Bin Sun 5,  Xuben Hou 6,  Hongxiang Lou 1
Affiliations

Affiliations

  • 1 Department of Natural Product Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.
  • 2 Institute of Medical Science, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.
  • 3 School of Pharmacy, Linyi University, Linyi, Shandong Province, China.
  • 4 The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.
  • 5 National Glycoengineering Research Center, Shandong University, Jinan, Shandong Province, China.
  • 6 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.
PMID: 36525499 DOI: 10.1126/sciadv.add5366
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.

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