The PDR-type ABC transporters AtrA and AtrG are involved in azole drug resistance in <i>Aspergillus oryzae</i>

For strain improvement of <i>Aspergillus oryzae</i>, development of the transformation system is essential, wherein dominant selectable markers, including drug-resistant genes, are available. However, <i>A. oryzae</i> generally has a relatively high resistance to many antifungal drugs effective against yeasts and other filamentous fungi. In the course of the study, while investigating azole drug resistance in <i>A. oryzae</i>, we isolated a spontaneous mutant that exhibited high resistance to azole fungicides and found that pleiotropic drug resistance (PDR)-type ATP-binding cassette (ABC) transporter genes were upregulated in the mutant; their overexpression in the wild-type strain increased azole drug resistance. While deletion of the gene designated <i>atrG</i> resulted in increased azole susceptibility, double deletion of <i>atrG</i> and another gene (<i>atrA</i>) resulted in further azole hypersensitivity. Overall, these results indicate that the ABC transporters AtrA and AtrG are involved in azole drug resistance in <i>A. oryzae</i>. ABC transporters AtrG and AtrA are involved in the azole drug resistance possibly by their drug efflux activities in <i>A. oryzae</i>.