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人类真菌病原体耐药性的实验进化。

Experimental evolution of drug resistance in human fungal pathogens.

机构信息

Department of Microbiology, The University of Manitoba, 45 Chancellor Circle, 213 Buller Building, R3T 2N2, Canada; Department of Statistics, The University of Manitoba, 45 Chancellor Circle, 318 Machray Hall, R3T 2N2, Canada.

Department of Microbiology, The University of Manitoba, 45 Chancellor Circle, 213 Buller Building, R3T 2N2, Canada.

出版信息

Curr Opin Genet Dev. 2022 Oct;76:101965. doi: 10.1016/j.gde.2022.101965. Epub 2022 Aug 8.

Abstract

Experimental evolution in vitro is a powerful tool to uncover the factors that contribute to resistance evolution and understand the genetic basis of adaptation. Here, we discuss recent experimental evolution studies from human fungal pathogens. We synthesize the results to highlight the common threads that influence resistance acquisition. The picture that emerges is that drug resistance consistently appears readily and rapidly. Mutations are often found in an overlapping set of genes and genetic pathways known to be involved in drug resistance, including whole or partial chromosomal aneuploidy. The likelihood of acquiring resistance and cross-resistance between drugs seems to be influenced by the specific drug (not just drug class), level of drug, and strain genetic background. We discuss open questions, such as the potential for increases in drug tolerance to evolve in static drugs. We highlight opportunities to use this framework to probe how different factors influence the rate and nature of adaptation to antifungal drugs in fungal microbes through a call for increased reporting on all replicates that were evolved, not just those that acquired resistance.

摘要

体外实验进化是揭示导致耐药性进化的因素和理解适应遗传基础的有力工具。在这里,我们讨论了来自人类真菌病原体的最近的实验进化研究。我们综合了这些结果,突出了影响耐药性获得的共同线索。出现的情况是,耐药性总是很容易且迅速地出现。突变通常发生在一组已知与耐药性相关的重叠基因和遗传途径中,包括整个或部分染色体非整倍性。获得耐药性的可能性以及药物之间的交叉耐药性似乎受到特定药物(不仅仅是药物类别)、药物水平和菌株遗传背景的影响。我们讨论了一些悬而未决的问题,例如在静态药物中,药物耐受性增加的可能性。我们强调了利用这一框架的机会,通过呼吁增加对所有进化的重复实验的报告,而不仅仅是那些获得耐药性的重复实验,来探究不同因素如何影响真菌微生物对抗真菌药物的适应性的速度和性质。

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