Back to Search
Start Over
Azole resistance in Aspergillus fumigatus isolates from respiratory specimens in Lyon University Hospitals, France: prevalence and mechanisms involved
- Source :
- International Journal of Antimicrobial Agents, International Journal of Antimicrobial Agents, 2021, 58 (6), pp.106447. ⟨10.1016/j.ijantimicag.2021.106447⟩
- Publication Year :
- 2021
-
Abstract
- Resistance of Aspergillus fumigatus to triazoles has been reported increasingly in Europe. As few data are available from Southern France, the objectives of this study were to assess the burden of A. fumigatus isolates with azole resistance from clinical specimens in Lyon, and explore the resistance mechanisms involved. In this retrospective cross-sectional study, 221 consecutive A. fumigatus isolates from respiratory samples were identified from an 8-month period from 195 patients attending the Pulmonary Medicine Departments of Lyon University Hospitals. Morphological identification was confirmed by sequence analysis of the β-tubulin gene. All samples were tested for susceptibilities to itraconazole, voriconazole, posaconazole and isavuconazole using concentration gradient strips, and the results were confirmed using the EUCAST broth microdilution method. Resistance mechanisms were investigated by sequencing the cyp51A gene and its promoter, and by expression analysis of cyp51 and genes encoding several efflux transporters. Four isolates exhibited azole resistance. Three isolates presented with polymorphisms in an intronic region of cyp51A, and one isolate had F46Y, M172V and E427K polymorphisms. No mutations were identified in the cyp51A promoter, but significant induction of cyp51A and cyp51B gene expression was observed for all four and three isolates, respectively. Significant induction of atrF and cdr1B gene expression was observed for two and three isolates, respectively. No significant induction of MDR1/2/3/4, MFS56 and M85 gene expression was observed. To conclude, the observed prevalence of azole resistance was 2.1%. Significant induction of expression of the cyp51 genes and two genes encoding efflux transporters was evidenced, underlying the diversity of resistance mechanisms to be explored.
- Subjects :
- Microbiology (medical)
Posaconazole
Antifungal Agents
Sequence analysis
Itraconazole
Pyridines
[SDV]Life Sciences [q-bio]
Microbial Sensitivity Tests
Polymorphism, Single Nucleotide
Microbiology
Aspergillus fumigatus
Fungal Proteins
Hospitals, University
Cytochrome P-450 Enzyme System
Tubulin
Gene expression
Nitriles
medicine
Humans
Pharmacology (medical)
Promoter Regions, Genetic
Gene
Respiratory Tract Infections
Retrospective Studies
Voriconazole
biology
Broth microdilution
General Medicine
Triazoles
biology.organism_classification
Infectious Diseases
Cross-Sectional Studies
France
medicine.drug
Subjects
Details
- ISSN :
- 18727913 and 09248579
- Volume :
- 58
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- International journal of antimicrobial agents
- Accession number :
- edsair.doi.dedup.....3987fe214344110e08072e211a1f5594