Elevated mutation rates in multi-azole resistant Aspergillus fumigatus drive rapid evolution of antifungal resistance.

ABSTRACT: The environmental use of azole fungicides has led to selective sweeps across multiple loci in the Aspergillus fumigatus genome causing the rapid global expansion of a genetically distinct cluster of resistant genotypes. Isolates within this cluster are also more likely to be resistant to agricultural antifungals with unrelated modes of action. Here we show that this cluster is not only multi-azole resistant but has increased propensity to develop resistance to next generation antifungals because of variants in the DNA mismatch repair system. A variant in msh6-G233A is found almost exclusively within azole resistant isolates harbouring the canonical cyp51A azole resistance allelic variant TR₃₄/L98H. Naturally occurring isolates with this msh6 variant display up to 5-times higher

SUBMITTER: Bottery MJ 

PROVIDER: S-EPMC11649685 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature