唑类耐药基因缺失导致临床分离株对唑类药物敏感性增强。
Abrogation of Triazole Resistance upon Deletion of in a Clinical Isolate of .
机构信息
University of Tennessee Health Science Center, Department of Clinical Pharmacy and Translational Science, Memphis, Tennessee, USA.
University of Tennessee Health Science Center, Department of Clinical Pharmacy and Translational Science, Memphis, Tennessee, USA
出版信息
Antimicrob Agents Chemother. 2019 Mar 27;63(4). doi: 10.1128/AAC.00057-19. Print 2019 Apr.
Abstract
has rapidly emerged as a health care-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four genes with the highest degree of homology to and among three triazole-resistant clinical isolates as compared to the triazole-susceptible genome reference clinical isolate. We subsequently utilized a novel Cas9-mediated system for genetic manipulations to delete and in both a triazole-resistant clinical isolate and a susceptible reference strain and observed that MICs for all clinically available triazoles decreased as much as 128-fold in the deletion strains. The findings of this work reveal for the first time that and are more highly expressed among triazole-resistant clinical isolates of and that the overexpression of is a significant contributor to clinical triazole resistance.
摘要
已迅速成为一种与医疗保健相关的、具有全球关注的多药耐药病原体。在这项工作中，我们研究了与 和 具有最高同源性的四个基因在三个唑类耐药临床分离株中的相对表达水平，与唑类敏感的基因组参考临床分离株相比。随后，我们利用一种新的 Cas9 介导的遗传操作系统，分别对唑类耐药临床分离株和敏感参考株中的 和 进行缺失，结果发现所有临床可用的唑类药物的 MIC 值在 缺失株中降低了多达 128 倍。这项工作的结果首次揭示了 和 中唑类耐药临床分离株中 和 的表达水平更高，并且 的过表达是导致临床唑类耐药的一个重要因素。
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