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.

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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