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 | Zendy

Cristina JiménezOrtigosa | Zendy; Winder B. Perez | Zendy; David Angulo | Zendy; Katyna Borroto–Esoda | Zendy; David S. Perlin | Zendy

Open Access

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

Author(s) -

Cristina JiménezOrtigosa,

Winder B. Perez,

David Angulo,

Katyna Borroto–Esoda,

David S. Perlin

Publication year - 2017

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.00833-17

Subject(s) - echinocandins , candida glabrata , echinocandin , broth microdilution , biology , microbiology and biotechnology , drug resistance , in vitro , minimum inhibitory concentration , candida albicans , antifungal , genetics , amphotericin b , fluconazole , caspofungin

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-resistantCandida glabrata isolates following drug exposurein vitro . Resistant isolates were analyzed using broth microdilution methodology andFKS 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.

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