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Genomic Approaches to Antifungal Drug Target Identification and Validation

Journal

ANNUAL REVIEW OF MICROBIOLOGY
Volume 76, Issue -, Pages 369-388

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev-micro-041020-094524

Keywords

chemical genomics; fungal pathogens; Candida; Cryptococcus; antifungal; Saccharomyces cerevisiae

Categories

Funding

  1. Canadian Institutes of Health Research Foundation [FDN-154288]
  2. National Institutes of Health NIAID [R01AI127375, R01AI162789, R01AI120958]

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In the past few decades, there has been a significant increase in drug-resistant fungal infections, posing a serious threat to human health. However, scientific advancements have provided hope for the discovery of new antifungal drugs. The use of chemical-genomic assays in Saccharomyces cerevisiae and molecular biology techniques in fungal pathogens has allowed for the identification and study of target genes for drug candidates, as well as the understanding of virulence attributes in diverse fungal pathogens, thus strengthening the development of antifungal drugs.
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 Saccharomyces cerevisiae 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 Candida albicans and Cryptococcus neoformans. 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.

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