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

Summary

Agricultural fungicides can cause fungal pathogens like Candida tropicalis to change their genetic structure and become resistant to clinical antifungal drugs. When exposed to agricultural azole fungicides, these fungi can shift from their normal two-copy genetic state to a one-copy state, making them harder to treat with hospital medicines. This study reveals how the same drugs used on farms can create dangerous drug-resistant fungi that threaten human health.

Background

Azoles are widely used antifungals in clinical settings and as major components of agricultural fungicides globally. Candida tropicalis is an opportunistic fungal pathogen classified as high-priority by the WHO, with invasive infections associated with 55-60% mortality rates and high azole resistance. Previous studies indicate that exposure to agricultural azoles in natural environments can facilitate emergence of clinical azole resistance.

Objective

To investigate novel mechanisms underlying acquired azole resistance in Candida tropicalis and understand how agricultural azole fungicides lead to emergence of drug-resistant strains exhibiting cross-resistance to clinical azoles.

Results

TBZ-resistant colonies exhibited multiple ploidy states including haploid (n), triploid (3n), aneuploid, and segmental aneuploid cells, with haploid cells showing cross-resistance to both agricultural and clinical azoles. Haploid cells were mating-competent and could mate with various ploidy states, showing slower growth and reduced virulence. Copy number variations in TAC1 and ERG11 genes were identified as contributing to azole resistance.

Conclusion

Ploidy plasticity, particularly the induction of haploid cell formation by agricultural azoles, represents a novel mechanism for azole resistance in C. tropicalis with implications for clinical resistance. The ability of haploid cells to mate and generate various ploidy states may be an evolutionary arsenal enabling C. tropicalis to become one of the most successful drug-resistant fungal pathogens.
  • Published in:PLoS Biology,
  • Study Type:Primer/Commentary on Research Study,
  • Source: PMID: 40173118, DOI: 10.1371/journal.pbio.3003083
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