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 β-(1,3)-d-glucan synthase (GS). We evaluated the spontaneous emergence of SCY-078-resistant isolates following drug exposure Resistant isolates were analyzed using broth microdilution methodology and sequencing. The kinetic inhibition parame...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2017-09, Vol.61 (9)
Main Authors: Jiménez-Ortigosa, Cristina, Perez, Winder B, Angulo, David, Borroto-Esoda, Katyna, Perlin, David S
Format: Article
Language:English
Subjects:
Antifungal Agents
Antifungal Agents - pharmacology
Candida glabrata
Candida glabrata - drug effects
Candida glabrata - genetics
Candidiasis - drug therapy
Candidiasis - microbiology
Drug Resistance, Fungal
Drug Resistance, Fungal - drug effects
Drug Resistance, Fungal - genetics
Echinocandins
Echinocandins - pharmacology
Fungal Proteins
Fungal Proteins - genetics
Glucosyltransferases - genetics
Glycosides
Glycosides - pharmacology
Humans
Mechanisms of Resistance
Microbial Sensitivity Tests - methods
Mutation
Mutation - drug effects
Triterpenes
Triterpenes - pharmacology
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Summary: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 isolates following drug exposure Resistant isolates were analyzed using broth microdilution methodology and sequencing. The kinetic inhibition parameter IC (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.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.00833-17