Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Antimicrob Agents Chemother. 2011 Aug;55(8):3947-9. doi: 10.1128/AAC.00044-11. Epub 2011 May 31.
Echinocandins, including caspofungin (CSP) and micafungin (MCF), are highly active versus Candida glabrata (MIC of ≤0.06 μg/ml). True resistance (MIC of ≥1 μg/ml) is a rare event and strictly associated with mutations in β-1,3-glucan synthase gene FKS1 or FKS2. In contrast, we show here that mutants exhibiting reduced susceptibility to CSP (CRS; MICs of 0.12 to 0.5 μg/ml) are readily selected in vitro and, paradoxically, demonstrate increased susceptibility to MCF (MIS) ranging from 4- to 32-fold. CRS-MIS mutants were generated from all 10 C. glabrata strains tested and were tentatively identified within a collection of clinical isolates. Intriguingly, sequencing and gene disruption demonstrated that CRS-MIS is Fks independent.
棘白菌素类，包括卡泊芬净（CSP）和米卡芬净（MCF），对光滑念珠菌（MIC≤0.06μg/ml）具有高度活性。真正的耐药（MIC≥1μg/ml）是一种罕见的事件，并且与β-1,3-葡聚糖合成酶基因 FKS1 或 FKS2 的突变密切相关。相比之下，我们在这里表明，对 CSP 表现出降低敏感性的突变体（CRS；MIC 值为 0.12 至 0.5μg/ml）在体外很容易被选择，并且矛盾的是，对 MCF（MIS）的敏感性增加了 4 至 32 倍。CRS-MIS 突变体是从所有 10 株测试的光滑念珠菌菌株中产生的，并在一组临床分离株中被初步鉴定。有趣的是，测序和基因敲除表明 CRS-MIS 与 Fks 无关。
