Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.
Methods Mol Biol. 2023;2658:127-143. doi: 10.1007/978-1-0716-3155-3_9.
Drug target identification is an essential component to antifungal drug development. Many methods, including large chemical library screening, natural product screening, and drug repurposing efforts, can identify compounds with favorable in vitro antifungal activity. However, these approaches will often identify compounds with no known mechanism of action. Herein, we describe a method utilizing the human fungal pathogen Cryptococcus neoformans to identify antifungal drug targets through the isolation of spontaneous resistant mutants, antifungal testing, whole-genome sequencing, and variant analysis.
药物靶点的鉴定是抗真菌药物开发的重要组成部分。许多方法，包括大型化学文库筛选、天然产物筛选和药物再利用努力，可以鉴定具有良好体外抗真菌活性的化合物。然而，这些方法通常会鉴定出具有未知作用机制的化合物。在此，我们描述了一种利用人类真菌病原体新型隐球菌通过分离自发耐药突变体、抗真菌测试、全基因组测序和变异分析来鉴定抗真菌药物靶点的方法。
