Epigenetic Regulation of Antifungal Drug Resistance

Abstract

In medical mycology, epigenetic mechanisms are emerging as key regulators of multiple aspects of fungal biology ranging from development, phenotypic and morphological plasticity to antifungal drug resistance. Emerging resistance to the limited therapeutic options for the treatment of invasive fungal infections is a growing concern. Human fungal pathogens develop drug resistance via multiple mechanisms, with recent studies highlighting the role of epigenetic changes involving the acetylation and methylation of histones, remodeling of chromatin and heterochromatin-based gene silencing, in the acquisition of antifungal resistance. A comprehensive understanding of how pathogens acquire drug resistance will aid the development of new antifungal therapies as well as increase the efficacy of current antifungals by blocking common drug-resistance mechanisms. In this article, we describe the epigenetic mechanisms that affect resistance towards widely used systemic antifungal drugs: azoles, echinocandins and polyenes. Additionally, we review the literature on the possible links between DNA mismatch repair, gene silencing and drug-resistance mechanisms.

Keywords

• histones
• histone methylation and acetylation
• chromatin
• multidrug transporter
• azoles
• echinocandins and polyenes