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PMID: 15215142 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Substitutions at methionine 220 in the 14alpha-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs.

Antimicrobial agents and chemotherapy ·Vol. 48 ·No. 7 ·2004-07-00 ·Pages 2747-50

Mellado E, Garcia-Effron G, Alcazar-Fuoli L, Cuenca-Estrella M, Rodriguez-Tudela JL

Abstract

Five clinical isolates of Aspergillus fumigatus that exhibited similar patterns of reduced susceptibility to itraconazole and other triazole drugs were analyzed. Sequence analysis of genes (cyp51A and cyp51B) encoding the 14alpha-sterol demethylases revealed that all five strains harbored mutations in cyp51A resulting in the replacement of methionine at residue 220 by valine, lysine, or threonine. When the mutated cyp51A genes were introduced into an A. fumigatus wild-type strain, the transformants exhibited reduced susceptibility to all triazole agents, confirming that the mutations were responsible for the resistance phenotype.

MeSH Terms
Alleles Amino Acid Sequence Amino Acid Substitution Antifungal Agents/pharmacology Aspergillus fumigatus/enzymology,genetics Azoles/pharmacology Cytochrome P-450 Enzyme System/genetics Drug Resistance, Fungal Fungal Proteins/genetics Methionine/metabolism Microbial Sensitivity Tests Molecular Sequence Data Mutation/genetics Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Antifungal Agents Azoles Fungal Proteins Cytochrome P-450 Enzyme System Methionine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mellado E
Servicio de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, Spain. [email protected]
Garcia-Effron G
Alcazar-Fuoli L
Cuenca-Estrella M
Rodriguez-Tudela J L
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.48.7.2747-2750.2004
Email
[email protected]
Published
2004-07-00
Pages
2747-50
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC434164
Subset
IM
External Links
PubMed source DOI: 10.1128/AAC.48.7.2747-2750.2004 PMC Full Text View journal details
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