The mitochondrial protein Bcs1A regulates antifungal drug tolerance by affecting efflux pump expression in the filamentous pathogenic fungus Aspergillus fumigatus

Abstract

Drug resistance presents a formidable obstacle in the clinical management of aspergillosis. Mitochondria are integral to various biochemical pathways, including those involved in fungi drug response, making mitochondrial proteins promising therapeutic targets for drug therapy. This study confirms that Bcs1A, a mitochondrial respiratory chain protein, is indispensable for mitochondrial functionality and multidrug tolerance in Aspergillus fumigatus . Mutation of Bcs1A not only leads to a series of drug efflux pumps upregulated but also shows that loss of the primary efflux pump, mdr1 , partial reduction in drug tolerance in the Bcs1A mutant, highlighting that Bcs1A’s significant influence on mitochondria-mediated drug resistance.