Contributions of yap1 Mutation and Subsequent atrF Upregulation to Voriconazole Resistance in Aspergillus flavus.

ABSTRACT: Aspergillus flavus is the second most significant pathogenic cause of invasive aspergillosis; however, its emergence risks and mechanisms of voriconazole (VRC) resistance have not yet been elucidated in detail. Here, we demonstrate that repeated exposure of A. flavus to subinhibitory concentrations of VRC in vitro causes the emergence of a VRC-resistant mutant with a novel resistance mechanism. The VRC-resistant mutant shows a MIC of 16 μg/ml for VRC and of 0.5 μg/ml for itraconazole (ITC). Whole-genome sequencing analysis showed that the mutant possesses a point mutation in yap1, which encodes a bZIP transcription factor working as the master regulator of the oxidative stress response, but no mutations in the cyp51 genes. This point mutation in yap1</

SUBMITTER: Ukai Y 

PROVIDER: S-EPMC6201102 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature