光滑念珠菌获得对 SCY-078 的耐药性涉及 FKS 突变，这些突变既重叠又不同于那些赋予棘白菌素类耐药性的突变。
Acquisition of Resistance to SCY-078 in Candida glabrata Involves FKS Mutations That both Overlap and Are Distinct from Those Conferring Echinocandin Resistance.
机构信息
Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA.
Scynexis, Inc., Jersey City, New Jersey, USA.
出版信息
Antimicrob Agents Chemother. 2017 Aug 24;61(9). doi: 10.1128/AAC.00833-17. Print 2017 Sep.
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 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.
摘要
SCY-078 是一种具有口服活性的抗真菌药物，其靶标是 β-(1,3)-d-葡聚糖合成酶 (GS)。我们评估了药物暴露后 SCY-078 耐药株的自发出现情况。耐药株的分析采用肉汤微量稀释法和测序。GS 复合物的动力学抑制参数 IC（50%抑制浓度）也得到了确定。发现的耐药突变谱表明，相对于棘白菌素，SCY-078 在 GS 上的结合位点部分重叠但独立。
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