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

Summary

Farmers use a fungicide called tebuconazole to protect crops, but this chemical is similar to medicines doctors use to treat serious fungal infections in patients. A new study shows that when the fungus Aspergillus fumigatus is exposed to tebuconazole, it becomes resistant not just to this pesticide, but also to the clinical antifungal drugs used in hospitals. The fungus develops resistance mechanisms that allow it to survive high doses of these medications. This research highlights an important public health concern: the overuse of similar chemicals in agriculture can undermine our ability to treat dangerous fungal infections in people.

Background

Multiazole-resistant Aspergillus fumigatus threatens antifungal therapy effectiveness. Agricultural triazoles like tebuconazole share chemical structural similarity with clinical triazoles, potentially inducing cross-resistance in fungal populations.

Objective

This study investigated the impact of prolonged exposure to the agricultural triazole tebuconazole (TEB) on A. fumigatus susceptibility to clinical triazoles and identified the resistance mechanisms involved.

Results

After 28 days, resistant strains emerged with MIC increases up to 128× for itraconazole, 64× for posaconazole, and 16× for voriconazole. Resistance was maintained in the absence of TEB and associated with maintained ergosterol levels, efflux pump activity, and upregulation of 193 proteins including those related to resistance pathways.

Conclusion

Agricultural triazole exposure induces stable multidrug-resistant phenotypes in A. fumigatus through multiple mechanisms including efflux pump activation and target enzyme modifications. Continuous monitoring of triazole pesticide application is urgently needed to minimize clinical resistance development.
  • Published in:ACS Omega,
  • Study Type:Experimental Laboratory Study,
  • Source: 10.1021/acsomega.5c07812; PMID: 41179170
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