新型非热点 Fks1 突变导致耳念珠菌对棘白菌素类药物的耐药性。
Novel Non-Hot Spot Modification in Fks1 of Candida auris Confers Echinocandin Resistance.
机构信息
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil.
出版信息
Antimicrob Agents Chemother. 2023 Jun 15;67(6):e0042323. doi: 10.1128/aac.00423-23. Epub 2023 May 24.
Abstract
We determined the echinocandin susceptibility and genotypes of 13 clinical isolates of Candida auris that were recovered from 4 patients at a tertiary care center in Salvador, Brazil. Three isolates were categorized as echinocandin-resistant, and they harbored a novel mutation that led to an amino acid change W691L located downstream from hot spot 1. When introduced to echinocandin-susceptible C. auris strains by CRISPR/Cas9, Fks1 W691L induced elevated MIC values to all echinocandins (anidulafungin, 16 to 32×; caspofungin, >64×; micafungin, >64×).
摘要
我们从巴西萨尔瓦多一家三级保健中心的 4 名患者身上分离出 13 株临床分离的耳念珠菌，确定了它们对棘白菌素的敏感性和基因型。3 株被归类为棘白菌素耐药，它们携带一种新的突变，导致位于热点 1 下游的氨基酸改变 W691L。当通过 CRISPR/Cas9 引入到对棘白菌素敏感的耳念珠菌菌株中时，Fks1 W691L 导致所有棘白菌素（安尼卡fungin，16 至 32×；卡泊芬净，>64×；米卡芬净，>64×）的 MIC 值升高。
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