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Moving beyond multi-triazole to multi-fungicide resistance: Broader selection of drug resistance in the human fungal pathogen Aspergillus fumigatus

Summary

Aspergillus fumigatus is a dangerous fungal infection treated with triazole drugs, but the fungus is developing resistance to multiple antifungal medications. This resistance appears to be selected in agricultural settings where fungicides are used on crops, and resistant strains then spread to humans through the air. The problem is worse because agricultural fungicides are selecting for strains resistant to multiple drug classes at once, making infections harder to treat. Addressing this issue requires reducing fungicide use in agriculture and better strategies for managing antifungal resistance.

Background

Aspergillus fumigatus is a ubiquitous fungal pathogen causing serious infections in immunocompromised individuals. Triazole antifungals are the first-line treatment, targeting ergosterol synthesis pathways. The emergence of multi-triazole-resistant A. fumigatus strains linked to agricultural fungicide use has become a critical clinical concern.

Objective

To examine how the dual use of antifungal compounds in agriculture and medicine contributes to the development of multi-fungicide resistance in A. fumigatus. The paper discusses mechanisms of resistance selection beyond triazoles, including MBCs, SDHIs, and QoIs.

Results

Evidence demonstrates that triazole-resistant A. fumigatus isolates frequently harbor co-resistance mutations to non-triazole fungicides (MBCs, QoIs, SDHIs). Agricultural fungicide residues in decomposing organic matter create environmental niches selecting for multi-fungicide-resistant strains. Multi-fungicide-resistant strains show no apparent fitness cost, possibly due to compensatory mutations.

Conclusion

Agricultural use of multiple fungicide classes creates selection pressure for broadly multi-fungicide-resistant A. fumigatus strains that can disperse environmentally. Future antifungal resistance research must extend beyond triazoles to examine non-azole fungicides, and new strategies addressing environmental selection pressures are essential to combat this growing clinical challenge.
  • Published in:PLoS Pathog,
  • Study Type:Review,
  • Source: PMID: 39928648, DOI: 10.1371/journal.ppat.1012851
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