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Mechanisms to reduce the cytotoxicity of pharmacological nicotinamide concentrations in the pathogenic fungus Candida albicans
Author(s) -
Ghugari Rahul,
Tsao Sarah,
Schmidt Mark,
Bonneil Éric,
Brenner Charles,
Verreault Alain
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15622
Subject(s) - candida albicans , nad+ kinase , biology , sirtuin , corpus albicans , cytotoxicity , nicotinamide , intracellular , metabolome , sirtuin 1 , microbiology and biotechnology , acetylation , histone deacetylase , biochemistry , metabolite , histone , in vitro , downregulation and upregulation , enzyme , gene
Inhibition of the fungal‐specific sirtuin Hst3 with nicotinamide (NAM) is cytotoxic to Candida albicans and other pathogenic fungi. We show that ‘pharmacological’ NAM has three fates in C. albicans . First, NAM can come out of cells. Second, NAM enters a salvage pathway that generates NAD + . Third, NAM is incorporated into NAD + through a NAM exchange reaction. Our findings raise important challenges about the future of NAM as antifungal agent.