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cyp51A Mutations, Extrolite Profiles, and Antifungal Susceptibility in Clinical and Environmental Isolates of the Aspergillus viridinutans Species Complex
- Source :
- Antimicrobial Agents and Chemotherapy, Antimicrobial Agents and Chemotherapy, 63, Antimicrobial Agents and Chemotherapy, 63, 11, Talbot, J J, Frisvad, J C, Meis, J F, Hagen, F, Verweij, P E, Hibbs, D E, Lai, F, Samson, R A, Kidd, S E, Barrs, V R & Houbraken, J 2019, ' Cyp51A mutations, Extrolite Profiles and Antifungal Susceptibility in Clinical and Environmental Isolates of the Aspergillus viridinutans Species Complex ', Antimicrobial Agents and Chemotherapy, vol. 63, no. 11, e00632-19 . https://doi.org/10.1128/AAC.00632-19, Antimicrobial Agents and Chemotherapy, 63(11). American Society for Microbiology
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- The past decade has seen an increase in aspergillosis in humans and animals due to Aspergillus viridinutans species complex members. Azole resistance is common to these infections, carrying a poor prognosis. cyp51A gene mutations are the main cause of acquired azole resistance in Aspergillus fumigatus. This study aimed to determine if the azole-resistant phenotype in A. viridinutans complex members is associated with cyp51A mutations or extrolite profiles.<br />The past decade has seen an increase in aspergillosis in humans and animals due to Aspergillus viridinutans species complex members. Azole resistance is common to these infections, carrying a poor prognosis. cyp51A gene mutations are the main cause of acquired azole resistance in Aspergillus fumigatus. This study aimed to determine if the azole-resistant phenotype in A. viridinutans complex members is associated with cyp51A mutations or extrolite profiles. The cyp51A gene of clinical and environmental isolates was amplified using novel primers, antifungal susceptibility was tested using the Clinical and Laboratory Standards Institute methodology, and extrolite profiling was performed using agar plug extraction. Very high azole MICs were detected in 84% of the isolates (31/37). The MICs of the newer antifungals luliconazole and olorofim (F901318) were low for all isolates. cyp51A sequences revealed 113 nonsynonymous mutations compared to the sequence of wild-type A. fumigatus. M172A/V and D255G, previously associated with A. fumigatus azole resistance, were common among all isolates but were not correlated with azole MICs. Two environmental isolates with nonsusceptibility to itraconazole and high MICs of voriconazole and isavuconazole harbored G138C, previously associated with azole-resistant A. fumigatus. Some novel mutations were identified only among isolates with high azole MICs. However, cyp51A homology modeling did not cause a significant protein structure change for these mutations. There was no correlation between extrolite patterns and susceptibility. For A. viridinutans complex isolates, cyp51A mutations and the extrolites that they produced were not major causes of antifungal resistance. Luliconazole and olorofim show promise for treating azole-resistant infections caused by these cryptic species.
- Subjects :
- Aspergillus viridinutans, Aspergillus felis, Aspergillus udagawae
Itraconazole
Luliconazole
Aspergillus udagawae
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Aspergillus felis
Gene mutation
Aspergillosis
Aspergillus fumigatus
Microbiology
03 medical and health sciences
chemistry.chemical_compound
All institutes and research themes of the Radboud University Medical Center
azole resistance
Aspergillus viridinutans
Mechanisms of Resistance
medicine
cyp51A
Pharmacology (medical)
030304 developmental biology
Pharmacology
chemistry.chemical_classification
Voriconazole
0303 health sciences
cryptic species
biology
030306 microbiology
medicine.disease
biology.organism_classification
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4]
Infectious Diseases
chemistry
Cryptic species
Azole resistance
Azole
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 10986596 and 00664804
- Volume :
- 63
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....467382cc10016764489906550685ad2c