Aspergillus Fumigatus CYP51 Sequence: Potential Basis for Fluconazole Resistance

Med Mycol. 2001 Jun;39(3):299-302. doi: 10.1080/mmy.39.3.299.302.

Abstract

We have cloned and sequenced the Aspergillus fumigatus CYP51 gene which encodes the target of azole antifungal agents, namely cytochrome P450 sterol 14alpha-demethylase. Since A. fumigatus is intrinsically resistant to the widely used azole fluconazole, we compared its predicted CYP51 sequence to the CYP51 sequences from fluconazole-susceptible and resistant Candida albicans. This analysis generated specific hypotheses regarding the basis for A. fumigatus fluconazole resistance; in particular, A. fumigatus residue Ile301 corresponds to C. albicans residue Thr315 which is mutated to Ala in resistant strains and is proposed to hydrogen bond with the sterol substrate.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antifungal Agents / pharmacology*
  • Aspergillus fumigatus / drug effects*
  • Aspergillus fumigatus / enzymology
  • Cloning, Molecular
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / genetics*
  • Drug Resistance, Fungal / genetics*
  • Fluconazole / pharmacology*
  • Molecular Sequence Data
  • Oxidoreductases / chemistry
  • Oxidoreductases / genetics*
  • Phylogeny
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sterol 14-Demethylase

Substances

  • Antifungal Agents
  • Fluconazole
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Sterol 14-Demethylase

Associated data

  • GENBANK/AF222068