Luciferase-Based High-Throughput Screen with Aspergillus fumigatus to Identify Antifungal Small Molecules

Abstract

Only three classes of contemporary antifungal drugs are routinely utilized in the clinic against filamentous fungal pathogens such as Aspergillus fumigatus. High-throughput phenotypic screens to identify small molecules with activity against filamentous fungi remain challenging due to the hyphal, biofilm-like growth morphology of these important organisms. In this chapter, we describe a protocol for utilizing a bioluminescent A. fumigatus strain for identifying small molecules that potentiate the activity of the triazole antifungal drug fluconazole. The assay holds great promise for identifying small molecules with activity against filamentous fungal pathogens.

Keywords: Antifungal; Aspergillus fumigatus; Assay development; Filamentous fungi; High-throughput; Luminescence; Phenotypic screen; Small molecules.