Drug Transporter Mutants of Aspergillus nidulans as Tools in Fungicide Discovery

摘要

Membrane transporter proteins from filamentous fungi can function as drug transporters and may provide protection against natural toxic compounds from plants (plant defence compounds) and microorganisms (antibiotics), drugs (fungicides, antimycotics),and other toxic compounds. Overexpression of drug transporters can result in multidrug resistance (MDR) to unrelated compounds, while mutants with non-functional drug transporter genes may exhibit a hypersensitive phenotype. We have constructed a deletion mutant of Aspergillus nidulans with the non-functional ABC transporter genes atrB, atrD and atrG. This triple deletion mutant is hypersensitive to antibiotics (e.g. nigericin and valinomycin), plant compounds (e.g. camptothecin) and fungicides (e.g. azoles, anilino-pyrimidines, and phenylpyrroles). We propose that the mutant is a useful tester strain in discovery and development of lead products for novel antimycotics and fungicides. Overexpressants of drug transporters can be used as a tester strain to detect inhibitors of drug transporter activity (modulators). Inhibitors of ABC transporters that act as a virulence factor during pathogenesis can be regarded as potential disease control agents.