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Triazole-resistant Aspergillus fumigatus harbouring G54 mutation: Is it de novo or environmentally acquired?
Cheshta Sharma1, Ferry Hagen2, Ruxandra Moroti3
1Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110 007, India.
Abstract:
Triazole resistance in Aspergillus fumigatus develops in patients with chronic lung diseases receiving long-term azole therapy or by environmental selection of resistant A. fumigatus. Here we report for the first time the isolation of triazole-resistant A. fumigatus (TRAF) harbouring the G54E mutation from environmental samples in India, Romania and Tanzania. This mutation in the cyp51A azole target gene of A. fumigatus is so far considered as de novo occurring in patients due to prolonged exposure to azoles. A total of 81 soil and woody debris samples from India, Romania and Tanzania were processed for detection of TRAF and determination of their susceptibility to medical triazoles and fungicides. cyp51A sequencing and real-time PCR were performed for detection of mutations. The isolates were genotyped by microsatellite typing. Overall, 25% of samples (20/81) from India, Romania and Tanzania harboured TRAF. Of the 20 samples harbouring TRAF, a single resistance mechanism, the G54E mutation, was found in 16 samples from three countries. This mechanism was responsible for 46.4% of resistant isolates from Tanzania, 30.4% from Romania and 20.0% from India. The G54E isolates revealed high MICs of itraconazole and posaconazole and were cross-resistant to agricultural fungicides. The majority of the Romanian and Tanzanian G54E isolates had an identical genotype. The present report describes the genetic heterogeneity of TRAF strains harbouring the G54E mutation in the environment of India, Romania and Tanzania. It may be anticipated that long-term exposure of A. fumigatus to fungicides may induce selection of G54 mutants in the environment.
Insights
Triazole-resistant Aspergillus fumigatus (TRAF) with the G54E mutation was found in environmental samples across India, Romania, and Tanzania. This finding suggests environmental fungicide exposure may select for resistant fungal strains.
Area of Science:
- Environmental microbiology
- Medical mycology
- Fungal genetics
Background:
- Triazole resistance in Aspergillus fumigatus is a growing concern, often linked to patient azole therapy or environmental selection.
- The G54E mutation in the cyp51A gene was previously thought to arise primarily in patients undergoing prolonged azole treatment.
Purpose of the Study:
- To report the first isolation of triazole-resistant Aspergillus fumigatus (TRAF) harboring the G54E mutation from environmental sources in India, Romania, and Tanzania.
- To investigate the prevalence and characteristics of TRAF with the G54E mutation in diverse environmental settings.
Main Methods:
- Environmental soil and woody debris samples (n=81) from India, Romania, and Tanzania were analyzed.
- Detection of TRAF involved culturing, cyp51A gene sequencing, and real-time PCR for mutation identification.
- Isolate susceptibility to medical triazoles and agricultural fungicides was determined, alongside microsatellite genotyping.
Main Results:
- Triazole-resistant Aspergillus fumigigatus (TRAF) was detected in 25% (20/81) of environmental samples.
- The G54E mutation was identified as the sole resistance mechanism in 16 of the TRAF isolates across all three countries.
- G54E isolates exhibited high minimum inhibitory concentrations (MICs) for itraconazole and posaconazole and showed cross-resistance to agricultural fungicides.
Conclusions:
- The G54E mutation conferring triazole resistance in Aspergillus fumigatus is present in environmental samples from India, Romania, and Tanzania.
- Environmental selection pressure from agricultural fungicides may contribute to the emergence and spread of G54E mutants.
- Genetic analysis revealed heterogeneity among G54E strains, with some Romanian and Tanzanian isolates sharing identical genotypes.
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