Triazole resistance in Aspergillus fumigatu s isolated from a tomato production environment exposed to propiconazole

Appl Environ Microbiol. 2024 Apr 17;90(4):e0001724. doi: 10.1128/aem.00017-24. Epub 2024 Mar 27.

Abstract

The emergence of azole-resistant Aspergillus fumigatus (ARAf) across the world is an important public health concern. We sought to determine if propiconazole, a demethylase inhibitor (DMI) fungicide, exerted a selective pressure for ARAf in a tomato production environment following multiple exposures to the fungicide. A tomato field trial was established in 2019 and propiconazole was applied weekly until harvest. Soil, leaf, and fruit (when present) samples were collected at baseline and after each propiconazole application. A. fumigatus isolates (n, 178) were recovered and 173 were tested for susceptibility to itraconazole, posaconazole, voriconazole, and propiconazole in accordance with CLSI M38 guidelines. All the isolates were susceptible to medical triazoles and the propiconazole MIC ranged from 0.25 to 8 mg/L. A linear regression model was fitted that showed no longitudinal increment in the log2-fold azole MIC of the isolates collected after each propiconazole exposure compared to the baseline isolates. AsperGenius real-time multiplex assay ruled out TR34/L98H and TR46/Y121F/T289A cyp51A resistance markers in these isolates. Sequencing of a subset of isolates (n, 46) demonstrated widespread presence of F46Y/M172V/E427K and F46Y/M172V/N248T/D255E/E427K cyp51A mutations previously associated with reduced susceptibility to triazoles.

Importance: The agricultural use of azole fungicides to control plant diseases has been implicated as a major contributor to ARAf infections in humans. Our study did not reveal imposition of selection pressure for ARAf in a vegetable production system. However, more surveillance studies for ARAf in food crop production and other environments are warranted in understanding this public and One Health issue.

Keywords: Aspergillus fumigatus; One-Health; azole-resistance; azoles; cyp51A; demethylase inhibitors.

MeSH terms

  • Antifungal Agents / pharmacology
  • Aspergillus fumigatus / genetics
  • Azoles / pharmacology
  • Drug Resistance, Fungal / genetics
  • Fungal Proteins / genetics
  • Fungicides, Industrial* / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Solanum lycopersicum*
  • Triazoles / pharmacology
  • Vegetables

Substances

  • propiconazole
  • Azoles
  • Antifungal Agents
  • Fungal Proteins
  • Triazoles
  • Fungicides, Industrial