CYP51A polymorphisms of Aspergillus fumigatus in lung transplant recipients: Prevalence, correlation with phenotype, and impact on outcomes
| Autor: | Shahid Husain, Tony Mazzulli, Armelle Pérez-Cortés, Julianne V. Kus, Benoît Henry, Faiqa Cheema, Shaf Keshavjee, Lisa R. McTaggart, Alexis Guenette, Lianne G. Singer |
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| Rok vydání: | 2020 |
| Předmět: |
Antifungal Agents
medicine.medical_treatment Context (language use) Microbial Sensitivity Tests Aspergillosis Aspergillus fumigatus Fungal Proteins 03 medical and health sciences 0302 clinical medicine Cytochrome P-450 Enzyme System Genotype medicine Prevalence Lung transplantation Humans Point Mutation 030212 general & internal medicine Genotyping 0303 health sciences Aspergillus Polymorphism Genetic biology 030306 microbiology business.industry Broth microdilution General Medicine biology.organism_classification medicine.disease Transplant Recipients Infectious Diseases Phenotype Immunology business Lung Transplantation |
| Zdroj: | Medical mycology. 59(7) |
| ISSN: | 1460-2709 |
| Popis: | Azole resistance in Aspergillus fumigatus is increasing worldwide and can affect prognosis. It is mostly mediated by cytochrome P51 (CYP51) mutations. In lung transplant recipients (LTR), little is known regarding the prevalence and clinical impact of CYP51 mutations. One hundred thirty-one consecutive A. fumigatus isolates from 103 patients were subjected to CYP51A genotyping through PCR and sequencing. Antifungal susceptibility testing was performed using the Sensititre YeastOne YO-9© broth microdilution technique. Correlations between genotype, phenotype, clinical manifestations of Aspergillus infection, and clinical outcomes were made. Thirty-four (26%) isolates harbored mutations of CYP51A; N248K (n = 14) and A9T (n = 12) were the most frequent. Three isolates displayed multiple point mutations. No significant influences of mutational status were identified regarding azole MICs, the clinical presentation of Aspergillus disease, 1-year all-cause mortality, and clinical outcomes of invasive forms. In the specific context of lung transplant recipients, non-hotspot CYP51A-mutated isolates are regularly encountered; this does not result in major clinical consequences or therapeutic challenges.Lay SummaryIn 131 isolates of Aspergillus fumigatus isolates originating from 103 lung transplant recipients, the CYP51A polymorphism rate was 26%, mostly represented by N248K and A9T mutations. These mutations, however, did not significantly impact azoles minimal inhibitory concentrations or clinical outcomes. |
| Databáze: | OpenAIRE |
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