The cellular and molecular defense mechanisms of the Candida yeasts against azole antifungal drugs.

The molecular mechanisms supporting resistance to azole antifungals have attracted a great interest during the last decades because of the emergence of clinical resistance to the treatment of fungal infections. The availability of genome sequencing data, of molecular biology tools, and of a large set of clinical and laboratory azole-resistant strains, made the yeasts Candida the biological material of choice to decipher azole resistance mechanisms. The yeast Candida albicans has several cellular ways to resist to azole drugs: decreased affinity of the target protein Erg11p for the drugs, increased biosynthesis of Erg11p, and efflux of the drugs outside the fungal cells. At the molecular level, two main mechanisms are operating: point mutation in the target gene or in transcriptional activator factors, eventually associated to a loss of heterozygosity, and gene duplication that results from the extraordinary plasticity of the genome. This review proposes to explore the different molecular strategies that are used by Candida yeasts to fight azole antifungals.