ArticleAntimicrobial agents and chemotherapy2011
Interrogation of related clinical pan-azole-resistant Aspergillus fumigatus strains: G138C, Y431C, and G434C single nucleotide polymorphisms in cyp51A, upregulation of cyp51A, and integration and activation of transposon Atf1 in the cyp51A promoter.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Fusarium species,Scedosporium species, and Lomentospora prolificans: A systematic review to inform the World Health Organization priority list of fungal pathogens.Medical mycology · 2024Pooled it
- Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Guideline
- Antifungal Susceptibility andMicroorganisms · 2026Article
- Prevalence of cyp51A variants in a US collection of Aspergillus fumigatus clinical isolates and comparative analysis of their contribution to triazole antifungal resistance.The Journal of antimicrobial chemotherapy · 2026Article
- Most azole resistance mutations in the Candida albicans drug target confer cross-resistance without intrinsic fitness cost.Nature microbiology · 2024Article
- Isolation of triazole-resistantMycology · 2024Article
- Genomic Epidemiology Identifies Azole Resistance Due to TRJournal of fungi (Basel, Switzerland) · 2023Article
- Drug-ResistantPathogens (Basel, Switzerland) · 2023Review
- Fungal Drug Response and Antimicrobial Resistance.Journal of fungi (Basel, Switzerland) · 2023Review
- Article
- Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications.The Journal of antimicrobial chemotherapy · 2022Review
- Genetic Structure and Triazole Antifungal Susceptibilities of Alternaria alternata from Greenhouses in Kunming, China.Microbiology spectrum · 2022Article
- Long Terminal Repeat RetrotransposonAntimicrobial agents and chemotherapy · 2021Article
- Review
- A world-wide analysis of reduced sensitivity to DMI fungicides in the banana pathogen Pseudocercospora fijiensis.Pest management science · 2021Article
- Molecular Epidemiology ofJournal of fungi (Basel, Switzerland) · 2021Review
- Article
- Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates.Antimicrobial agents and chemotherapy · 2020Article
- A Collaborative Tale of Diagnosing and Treating Chronic Pulmonary Aspergillosis, from the Perspectives of Clinical Microbiologists, Surgical Pathologists, and Infectious Disease Clinicians.Journal of fungi (Basel, Switzerland) · 2020Review
- The Effect of Posaconazole, Itraconazole and Voriconazole in the Culture Medium onMicroorganisms · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
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Abstract
Multiple Aspergillus fumigatus isolates from a patient with two aspergillomas complicating chronic pulmonary aspergillosis were pan-azole resistant. Microsatellite typing was identical for all isolates despite major phenotypic and some growth rate differences. Three different cyp51A mutations were found (G138C, Y431C, and G434C), of which the first two were demonstrated by heterologous expression in a hypersusceptible Saccharomyces cerevisiae strain to be at least partly responsible for elevated MICs. cyp51A and cyp51B gene duplication was excluded, but increased expression of cyp51A was demonstrated in three isolates selected for additional study (7-to 13-fold increases). In the isolate with the greatest cyp51A expression, an Aft1 transposon was found inserted 370 bp upstream of the start codon of the cyp51A gene, an integration location never previously demonstrated in Aspergillus. Two transcription start sites were identified at 49 and 136 bp upstream of the start codon. The role of the Aft1 transposon, if any, in modulating cyp51A expression remains to be established. Increased mRNA expression of the transporters AfuMDR1 and AfuMDR4 also was demonstrated in some isolates, which could contribute to azole resistance or simply represent a stress response. The diversity of confirmed and possible azole resistance mechanisms demonstrated in a single series of isogenic isolates is remarkable, indicating the ability of A. fumigatus to adapt in the clinical setting.
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