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获得的全基因组DNA变化由白虫 (Candida albicans) 获得的Caspofungin适应突变体

Jeffrey Zuber¹, Sudisht K Sah¹, David H Mathews¹

¹Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA.

|August 26, 2023

概括

在Candida albicans中耐 Echinocandin (ECN) 耐药性是一个越来越令人担忧的问题. 这项研究在适应突变者中发现了112种独特的突变,揭示了可能导致ECN耐药性的途径.

科学领域:

菌类学菌类学是指菌类学.
遗传学遗传学是一个
药物耐药性药物耐药性药物耐药性

背景情况:

Echinocandins (ECNs) 是对Candida albicans感染的第一线治疗方法.
在C. albicans中增加的ECN耐药性需要了解耐药性机制.
ECN 抵抗是一种多阶段的进化过程.

研究的目的:

为了确定与C. albicans. ECN敏感性降低相关的DNA变化.
探索导致ECN耐药性演变的突变途径.

主要方法:

全球DNA测序四个实验室适应的C. albicans突变体,ECN敏感性降低.
分析开放式读取框架 (ORF) 和其他基因组特征中的和接近开放式读取框架 (ORF) 内的突变.

主要成果:

在两个替代突变途径中确定了112个独特的突变.
大约一半的突变和热点是独立的ECN适应突变体共享的.
在ORF,非ORF基因组特征 (例如,逆转移体,LTR) 和基因间区域中发现了突变.

结论:

在非相关药物适应突变体中重复发生的突变表明它们促进了ECN适应.
这些DNA变化可能会影响ECN易受性,从而导致药物耐药性的演变.
这些发现提供了超越经典FKS1突变驱动ECN抗性的机制的见解.

关键词:

在Candida albicans中使用.进行DNA分析.适应caspofungin的情况整个基因组的突变.单核酸替代物的流行率.

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