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

Summary

When farmers use antifungal pesticides called triazoles to protect crops, the fungi can develop resistance to these chemicals. This study found that when the fungus Aspergillus fumigatus is exposed to the agricultural triazole tebuconazole, it can become resistant not only to that pesticide but also to clinical triazole drugs used to treat human fungal infections. The resistant fungi maintain this resistance even when the pesticide is removed, suggesting that environmental pesticide use may threaten the effectiveness of medical antifungal treatments.

Background

Multiazole-resistant Aspergillus fumigatus is a significant threat to antifungal therapy. Agricultural triazoles and clinical triazoles share similar chemical structures and mechanisms of action, potentially leading to cross-resistance development in fungal pathogens.

Objective

To investigate the impact of prolonged exposure to the agricultural triazole tebuconazole on A. fumigatus susceptibility to clinical triazoles and identify the resistance mechanisms involved.

Results

Resistant strains emerged with up to 128-fold increase in itraconazole MIC, 64-fold for posaconazole, and 16-fold for voriconazole. Resistance was maintained without TEB exposure and associated with maintained CYP51A activity, stable ergosterol levels, and increased efflux pump activity. Proteomics identified 193 upregulated proteins including those related to ergosterol biosynthesis, efflux pumps, and heat shock response.

Conclusion

Agricultural triazole exposure induces stable multidrug-resistant phenotypes in A. fumigatus through ergosterol pathway maintenance and efflux pump upregulation, emphasizing the need for antifungal resistance surveillance in environmental and clinical settings.
  • Published in:ACS Omega,
  • Study Type:Laboratory Experimental Study,
  • Source: PMID: 41179170, DOI: 10.1021/acsomega.5c07812
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