Advances in fungal chemical genomics for the discovery of new antifungal agents,Annals of the New York Academy of Sciences

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Advances in fungal chemical genomics for the discovery of new antifungal agents
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2020-08-28 , DOI: 10.1111/nyas.14484
Alice Xue ₁ , Nicole Robbins ₁ , Leah E Cowen ₁

Affiliation

Invasive fungal infections have escalated from a rare curiosity to a major cause of human mortality around the globe. This is in part due to a scarcity in the number of antifungal drugs available to combat mycotic disease, making the discovery of novel bioactive compounds and determining their mode of action of utmost importance. The development and application of chemical genomic assays using the model yeast Saccharomyces cerevisiae has provided powerful methods to identify the mechanism of action of diverse molecules in a living cell. Furthermore, complementary assays are continually being developed in fungal pathogens, most notably Candida albicans and Cryptococcus neoformans, to elucidate compound mechanism of action directly in the pathogen of interest. Collectively, the suite of chemical genetic assays that have been developed in multiple fungal species enables the identification of candidate drug target genes, as well as genes involved in buffering drug target pathways, and genes involved in general cellular responses to small molecules. In this review, we examine current yeast chemical genomic assays and highlight how such resources provide powerful tools that can be utilized to bolster the antifungal pipeline.

中文翻译：

用于发现新抗真菌剂的真菌化学基因组学进展

侵袭性真菌感染已从罕见的好奇心升级为全球人类死亡的主要原因。这部分是由于可用于对抗真菌病的抗真菌药物数量稀缺，因此发现新的生物活性化合物并确定其作用方式至关重要。使用模型酵母Saccharomyces cerevisiae的化学基因组分析的开发和应用为鉴定活细胞中不同分子的作用机制提供了强有力的方法。此外，在真菌病原体中不断开发补充分析，最显着的是白色念珠菌和新型隐球菌，以阐明直接在感兴趣的病原体中的复合作用机制。总的来说，已经在多种真菌物种中开发的化学遗传分析套件能够识别候选药物靶基因，以及参与缓冲药物靶途径的基因，以及参与对小分子的一般细胞反应的基因。在这篇综述中，我们检查了当前的酵母化学基因组分析，并强调了这些资源如何提供强大的工具，可用于支持抗真菌管道。

更新日期：2020-08-28

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