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Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use?
Open accessAbstract
Invasive aspergillosis due to multi-azole-resistant Aspergillus fumigatus has emerged in the Netherlands since 1999, with 6.0-12.8% of patients harbouring resistant isolates. The presence of a single resistance mechanism (denoted by TR/L98H), which consists of a substitution at codon 98 of cyp51A and a 34-bp tandem repeat in the gene-promoter region, was found in over 90% of clinical A fumigatus isolates. This is consistent with a route of resistance development through exposure to azole compounds in the environment. Indeed, TR/L98H A fumigatus isolates were cultured from soil and compost, were shown to be cross-resistant to azole fungicides, and genetically related to clinical resistant isolates. Azoles are abundantly used in the environment and the presence of A fumigatus resistant to medical triazoles is a major challenge because of the possibility of worldwide spread of resistant isolates. Reports of TR/L98H in other European countries indicate that resistance might already be spreading.
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Metadata
- Authors
- Verweij, P. E., Snelders, E., Kema, G. H., Mellado, E., & Melchers, W. J.
- Affiliations
- Radboud University Medical Center (NL)
- Wageningen University & Research (NL)
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Verweij, Paul E
- Venue
- The Lancet Infectious Diseases
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 9
- Issue
- 12
- Pages
- 789-795
- ISSN
- 1473-3099 (ISSN-L)
- OpenAlex
- W2133000347
- Cited by
- 604
- References
- 52
- Citations by year
- 2026: 23 · 2025: 25 · 2024: 32 · 2023: 23 · 2022: 28 · 2021: 56 · 2020: 46 · 2019: 47 · 2018: 34 · 2017: 50 · 2016: 40 · 2015: 47 · 2014: 33 · 2013: 27 · 2012: 37
- FWCI
- 21.32
- Type
- journal article
- Language
- en
- Open access
- green
- research.wur.nl
- Locations
- The Lancet Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Pfizer
- Basilea Pharmaceutica
- Schering-Plough
- Gilead Sciences
- Cephalon
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Aspergillus fumigatus, azole resistance, invasive aspergillosis, cyp51A, triazole fungicides, cross-resistance, clinical isolates, resistance spread
- MeSH terms
- Antifungal Agents, Aspergillosis, Aspergillus fumigatus, Cytochrome P-450 Enzyme System, Europe, Fungal Proteins, Fungicides, Industrial, Humans, Microbial Sensitivity Tests, Mutation, Soil Microbiology, Triazoles, Drug Resistance, Multiple, Fungal
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