<i>De Novo</i> Acquisition of Resistance to SCY-078 in Candida glabrata Involves FKS Mutations That both Overlap and Are Distinct from Those Conferring Echinocandin Resistance

Abstract

SCY-078 is an orally active antifungal whose target is the β-(1,3)-d-glucan synthase (GS). We evaluated the spontaneous emergence of SCY-078-resistant <i>Candida glabrata</i> isolates following drug exposure <i>in vitro</i> Resistant isolates were analyzed using broth microdilution methodology and <i>FKS</i> sequencing. The kinetic inhibition parameter IC₅₀ (50% inhibitory concentration) was also determined from GS complexes. The spectrum of resistance mutations found suggested a partially overlapping but independent binding site for SCY-078 relative to echinocandins on GS.