A Point Mutation in the 14α-Sterol Demethylase Gene cyp51A Contributes to Itraconazole Resistance in Aspergillus fumigatus
Open accessAbstract
The genes encoding 14α-sterol demethylases ( cyp51A and cyp51B ) were analyzed in 12 itraconazole (ITC)-resistant and three ITC-susceptible clinical isolates of Aspergillus fumigatus . Six ITC-resistant strains exhibited a substitution of another amino acid for glycine at position 54, which is located at a very conserved region of the Cyp51A protein. The cyp51A gene from the A. fumigatus wild-type strain (CM-237) was replaced with the mutated cyp51A gene copy of an ITC-resistant strain (AF-72). Two transformants exhibited resistance to ITC, both of which had incorporated the mutated copy of the cyp51A gene.
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References 27 · Cited by 281
- Authors
- Diaz-Guerra, T. M., Mellado, E., Cuenca-Estrella, M., & Rodriguez-Tudela, J. L.
- Affiliations
- Unidad de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Mellado, E.
- ORCID
- Mellado, E.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2003-03
- Volume
- 47
- Issue
- 3
- Pages
- 1120-1124
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC149335
- OpenAlex
- W2101244261
- Cited by
- 281
- References
- 27
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 1 · 2023: 4 · 2022: 9 · 2021: 14 · 2020: 17 · 2019: 14 · 2018: 17 · 2017: 23 · 2016: 13 · 2015: 18 · 2014: 17 · 2013: 11 · 2012: 9
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Update notices
- correction (2004-03-01)
- Open access
- green
- europepmc.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- itraconazole resistance, Aspergillus fumigatus, cyp51A, point mutations, CYP51B, azole resistance, gene replacement, clinical isolates
- MeSH terms
- Antifungal Agents, Aspergillus fumigatus, Base Sequence, Cytochrome P-450 Enzyme System, Fungal Proteins, Microbial Sensitivity Tests, Molecular Sequence Data, Transformation, Genetic, Point Mutation, Itraconazole, Electroporation, Amino Acid Substitution, Reverse Transcriptase Polymerase Chain Reaction, Drug Resistance, Fungal
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