De novo acquisition of resistance to SCY-078 in Candida glabrata involves FKS mutations that both overlap and are distinct from those conferring echinocandin resistance

SCY-078 is an orally active antifungal whose target is the -(1,3)-D-glucan synthase (GS). We evaluated the spontaneous emergence of SCY-078-resistant Candida glabrata isolates following drug exposure in vitro. Resistant isolates were analyzed using broth microdilution methodology and FKS 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.