Truncated Afyap1 attenuates antifungal susceptibility of Aspergillus fumigatus to voriconazole and confers adaptation of the fungus to oxidative stress

Mycopathologia. 2010 Sep;170(3):155-60. doi: 10.1007/s11046-010-9309-2. Epub 2010 Apr 8.

Abstract

In yeasts truncated YAP1 homologues confer antifungal resistance. Our previous work has identified Afyap1, a YAP1 homologue, in Aspergillus fumigatus and found that it is responsible for oxidative stress in vitro. In order to decipher whether truncated Afyap1 involves in antifungal resistance mechanism and in oxidative stress adaptation in A. fumigatus, we introduce a putatively hyperactive truncated Afyap1 into wild-type A. fumigatus. We found that the resulted A. fumigatus containing truncated Afyap1 attenuated susceptibility to voriconazole and resistance to various oxidants. However, the Afyap1 deletion mutant and the strain harboring multiple copies of full-length Afyap1 had voriconazole susceptibility comparable with that of a wild-type A. fumigatus strain. Our study demonstrates that the truncated Afyap1 may involve in antifungal resistance to voriconazole in A. fumigatus and that the truncated Afyap1 sufficiently confers tolerance to oxidative stress in A. fumigatus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Antifungal Agents / pharmacology*
  • Aspergillus fumigatus / drug effects*
  • Aspergillus fumigatus / genetics
  • Drug Resistance, Fungal
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology*
  • Humans
  • Oxidative Stress*
  • Pyrimidines / pharmacology*
  • Sequence Deletion*
  • Stress, Physiological
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Triazoles / pharmacology*
  • Voriconazole

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Pyrimidines
  • Transcription Factors
  • Triazoles
  • Voriconazole