Role of FKS Gene in the Susceptibility of Pathogenic Fungi to Echinocandins

Abstract

Echinocandins are antifungal agents that specifically inhibit the biosynthesis of 1,3-β-D-glucan, a major structural component of fungal cell walls. Echinocandins are recommended as first-line or alternative/salvage therapy for candidiasis and aspergillosis in antifungal guidelines of various countries. Resistance to echinocandins has been reported in recent years. The mechanism of echinocandin resistance involves amino acid substitutions in hot spot regions of the FKS gene product, the catalytic subunit of 1,3-β-D-glucan synthase. This resistance mechanism contributes to not only acquired resistance in Candida spp., but also inherent resistance in some pathogenic fungi. An understanding of the echinocandin resistance mechanism is important to develop both effective diagnosis and treatment options for echinocandin-resistant fungal diseases.

Keywords: 1,3-β-D-glucan synthase; FKS; echinocandins; hot spot; resistance.