Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; email:
Annu Rev Microbiol. 2022 Sep 8;76:369-388. doi: 10.1146/annurev-micro-041020-094524. Epub 2022 Jun 1.
The last several decades have witnessed a surge in drug-resistant fungal infections that pose a serious threat to human health. While there is a limited arsenal of drugs that can be used to treat systemic infections, scientific advances have provided renewed optimism for the discovery of novel antifungals. The development of chemical-genomic assays using has provided powerful methods to identify the mechanism of action of molecules in a living cell. Advances in molecular biology techniques have enabled complementary assays to be developed in fungal pathogens, including and . These approaches enable the identification of target genes for drug candidates, as well as genes involved in buffering drug target pathways. Here, we examine yeast chemical-genomic assays and highlight how such resources can be utilized to predict the mechanisms of action of compounds, to study virulence attributes of diverse fungal pathogens, and to bolster the antifungal pipeline.
过去几十年见证了耐药真菌感染的激增，这些感染对人类健康构成了严重威胁。虽然有一些有限的药物可以用于治疗系统性感染，但科学的进步为发现新型抗真菌药物提供了新的乐观前景。使用化学基因组学测定方法的发展为鉴定活细胞中分子的作用机制提供了强大的方法。分子生物学技术的进步使得可以在真菌病原体中开发互补的测定方法，包括酿酒酵母和丝状真菌。这些方法可以识别候选药物的靶基因，以及参与缓冲药物靶途径的基因。在这里，我们研究了酵母化学基因组学测定方法，并强调了如何利用这些资源来预测化合物的作用机制，研究不同真菌病原体的毒力属性，并增强抗真菌药物的研发。
