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Azole resistance in a clinical isolate of Aspergillus fumigatus from Chile
Eduardo Álvarez Duarte1, Nicolás Cepeda2, Jean Miranda1
1Laboratorio Micología, ICBM - F. de Medicina, Universidad de Chile, Chile.
Background:
Aspergillus fumigatus is a ubiquitous opportunistic pathogen. This fungus can acquire resistance to azole antifungals due to different mutations in the cyp51A gene. Azole resistance has been observed in several continents and appears to be a globally distributed phenomenon. Specific mutations in cyp51A that lead to azole resistance, such as the TR34/L98H modification, have been reported.
Aims:
To evaluate the azole resistance in clinically isolated A. fumigatus strains.
Methods:
As a result of our passive surveillance strategy, a total of 23 A. fumigatus isolates from clinical origins were identified through a phylogenetic analysis using the ITS region and β-tubulin gene fragments, and typed with the CSP microsatellite. Azole susceptibility profiles were performed by disk diffusion and microdilution broth methodologies according to CLSI guidelines.
Results:
Here we describe, for the first time, the detection of azole-resistant A. fumigatus isolates from clinical origins in Chile with mutations in the cyp51A gene. In addition to the TR34/L98H mutation, one isolate exhibited an F46Y/M172V/E427K-type mutation. Furthermore, microsatellite typing based on cell surface protein (CSP) was performed, showing the t02 (TR34/L98H), t15 (F46Y/M172V/E427K) and t01 (susceptible clinical isolates) genotypes.
Conclusions:
Our study demonstrates the presence of mutations related to azole resistance in A. fumigatus strains isolated from clinical samples in Chile. In order to obtain information that may help to tackle the spread of antifungal resistance among A. fumigatus populations, and to ensure the efficacy of future treatments against aspergillosis, a further research is necessary.
Insights
Azole resistance in Aspergillus fumigatus is a growing global concern. This study detected azole-resistant strains with specific cyp51A gene mutations in clinical samples from Chile, highlighting the need for continued surveillance.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Molecular Biology
Background:
- Aspergillus fumigatus is a common opportunistic fungal pathogen.
- Acquired resistance to azole antifungals, driven by cyp51A gene mutations, is a significant global health issue.
- Specific mutations like TR34/L98H are known drivers of azole resistance.
Purpose of the Study:
- To investigate the prevalence of azole resistance in clinical Aspergillus fumigatus isolates.
- To identify specific genetic mutations associated with azole resistance in these isolates.
Main Methods:
- Phylogenetic analysis using ITS and beta-tubulin gene fragments for isolate identification.
- Microsatellite typing with cell surface protein (CSP) for genotyping.
- Azole susceptibility testing via disk diffusion and microdilution broth methods.
Main Results:
- Detection of azole-resistant Aspergillus fumigatus in clinical samples from Chile for the first time.
- Identification of the TR34/L98H mutation and a novel F46Y/M172V/E427K mutation in cyp51A.
- Genotyping revealed t02 (TR34/L98H) and t15 (F46Y/M172V/E427K) genotypes in resistant isolates.
Conclusions:
- Confirms the presence of azole resistance-associated mutations in clinical Aspergillus fumigatus from Chile.
- Underscores the importance of ongoing research to monitor and combat antifungal resistance.
- Emphasizes the need for strategies to ensure the effectiveness of azole treatments for aspergillosis.
