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

Cristina Jiménez-Ortigosa; Winder B. Perez; David Angulo; Katyna Borroto-Esoda; David S. Perlin

doi:10.1128/AAC.00833-17

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

Cristina Jiménez-Ortigosa
, Winder B. Perez
, David Angulo
, Katyna Borroto-Esoda
, David S. Perlin

Center for Discovery and Innovation

Hackensack Meridian School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	e00833-17
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	9
DOIs	https://doi.org/10.1128/AAC.00833-17
State	Published - Sep 2017

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

Keywords

Candida glabrata
Resistance
SCY-078

Access to Document

10.1128/AAC.00833-17

Cite this

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title = "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",

abstract = "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.",

keywords = "Candida glabrata, Resistance, SCY-078",

author = "Cristina Jim{\'e}nez-Ortigosa and Perez, \{Winder B.\} and David Angulo and Katyna Borroto-Esoda and Perlin, \{David S.\}",

year = "2017",

month = sep,

doi = "10.1128/AAC.00833-17",

language = "English",

volume = "61",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "9",

}

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. / Jiménez-Ortigosa, Cristina; Perez, Winder B.; Angulo, David et al.
In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 9, e00833-17, 09.2017.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Jiménez-Ortigosa, Cristina

AU - Perez, Winder B.

AU - Angulo, David

AU - Borroto-Esoda, Katyna

AU - Perlin, David S.

PY - 2017/9

Y1 - 2017/9

N2 - 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.

AB - 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.

KW - Candida glabrata

KW - Resistance

KW - SCY-078

UR - https://www.scopus.com/pages/publications/85028373625

U2 - 10.1128/AAC.00833-17

DO - 10.1128/AAC.00833-17

M3 - Article

C2 - 28630180

SN - 0066-4804

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 9

M1 - e00833-17

ER -

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

Abstract

UN SDGs

ASJC Scopus subject areas

Keywords

Access to Document

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