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Aspergillus fumigatus CYP51 sequence: potential basis for fluconazole resistance
Journal article   Peer reviewed

Aspergillus fumigatus CYP51 sequence: potential basis for fluconazole resistance

T D Edlind, K W Henry, K A Metera and S K Katiyar
Medical mycology (Oxford), v 39(3)
Jun 2001
PMID: 11446535

Abstract

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

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Web of Science research areas
Infectious Diseases
Mycology
Veterinary Sciences
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