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Ploidy plasticity drives fungal resistance to azoles used in agriculture and clinics

Summary

Agricultural fungicides called azoles can cause fungi to change their genetic makeup in ways that make them resistant to medical antifungal drugs. Researchers found that when Candida tropicalis (a fungal pathogen) is exposed to tebuconazole, an agricultural fungicide, it can transform into a haploid form (with half the normal chromosomes) that is resistant to both agricultural and clinical azoles. This discovery helps explain why fungal infections are becoming harder to treat in hospitals.

Background

The rapid increase in antifungal resistance is a major medical concern. Azoles are widely used as both clinical antifungals and agricultural fungicides globally. Previous studies suggest that exposure to agricultural azoles in natural environments can facilitate the emergence of clinical azole resistance in Candida tropicalis.

Objective

To investigate how agricultural azole fungicides lead to the emergence of drug-resistant strains of Candida tropicalis that exhibit cross-resistance to clinical azoles. The study aims to understand the novel mechanisms underlying acquired azole resistance in this opportunistic fungal pathogen.

Results

TBZ-resistant colonies exhibited various ploidy states including haploid (n), triploid (3n), aneuploid, and segmental aneuploid cells, representing a previously unknown haploid state for C. tropicalis. Haploid cells exhibited resistance to both agricultural and clinical azoles and were mating-competent. Copy number variations in azole resistance-related genes like TAC1 and ERG11 were identified.

Conclusion

Ploidy plasticity and the ability of haploid cells to undergo mating and generate various ploidy states represents a mechanism for emergence of drug-resistant strains. Isochromosome formation may be a general mechanism triggered by clinical and agricultural azoles that confers azole resistance across fungal species.
  • Published in:PLoS Biology,
  • Study Type:Experimental Evolution Study,
  • Source: 10.1371/journal.pbio.3003083, PMID: 40173118
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