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抗多醇耐药Aspergillus fumigatus的突变率较高,推动了抗真菌耐药性的快速演变

Michael J Bottery¹, Norman van Rhijn², Harry Chown^2,3

¹Manchester Fungal Infection Group, Division of Evolution, Infection, and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. michael.bottery@manchester.ac.uk.

Nature communications

|December 16, 2024

概括

阿斯伯吉勒斯烟虫的亚类真菌杀菌剂耐药性正在全球蔓延. 一种特定的突变 (msh6-G233A) 显著增加了突变率,加速了对新抗真菌药物耐药性的演变.

科学领域:

菌类学菌类学是指菌类学.
遗传学遗传学是一个
抗微生物耐药性抗微生物耐药性

背景情况:

环境醇真菌杀菌剂的使用推动了抗药性阿斯伯吉illus fumigatus基因型的全球扩散.
这些耐药菌株对具有不同作用模式的农业抗真菌药物表现出交叉耐药性.

研究的目的:

为了研究基因机制背后的多-azole耐药性和增加的倾向发展耐药性的下一代抗真菌药物在Aspergillus fumigatus.
为了确定与增强的抗真菌耐药性相关的特定遗传变异.

主要方法:

对Aspergillus fumigatus分离物的基因组分析.
基因变异的识别和表征,包括DNA不匹配修复系统 (例如msh6-G233A) 和cyp51A基因 (TR34/L98H) 的突变.
对具有特定遗传变异的分离物进行突变率分析.

主要成果:

一种msh6-G233A变异与携带TR34/L98H cyp51A等位基因的耐醇分离物密切相关.
具有msh6-G233A变异的分离物表现出高达5倍的突变率.
这种超级突变现象型没有可衡量的健身成本,并且已在全球传播.

结论:

与醇耐药性相关的msh6-G233A变体增强了对新抗真菌药物耐药性的演变.
这种变种的全球分布构成重大威胁,因为新型抗真菌药在临床和农业环境中可能有双重使用.

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