Exposure to Tebuconazole Drives Cross-Resistance to Clinical Triazoles in Aspergillus fumigatus

ABSTRACT: The emergence of triazole resistance in Aspergillus fumigatus poses a significant threat to clinical antifungal therapy. This study investigated the impact of prolonged exposure to the agricultural triazole tebuconazole (TEB) on the susceptibility of A. fumigatus to clinical triazoles and explored associated resistance mechanisms. After 28 days of exposure, isolates exhibited substantial increases in minimum inhibitory concentrations (MICs): up to 128-fold for itraconazole, 64-fold for posaconazole, and 16-fold for voriconazole. Resistance persisted even after TEB removal. Ergosterol levels remained stable, while efflux pump inhibition led to MIC reduction, confirming their role in resistance. Proteomic analysis identified 193 upregulated and 88 downregulated proteins, with distinct profiles between treated and untreated groups. These findings demonstrate that agricultural triazoles can induce stable, multidrug-resistant phenotypes in A. fumigatus, emphasizing the need for integrated surveillance of antifungal resistance across environmental and clinical settings.

INSTRUMENT(S):

ORGANISM(S): Neosartorya Fumigata (aspergillus Fumigatus)

TISSUE(S): Mycelium

SUBMITTER: Gonçalo Souza Filho  

LAB HEAD: Gonçalo Apolinário de Souza Filho

PROVIDER: PXD064657 | Pride | 2025-11-10

REPOSITORIES: Pride