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

Summary

Researchers discovered that a common agricultural fungicide can cause fungal cells to change their genetic structure in ways that make them resistant to medicines used to treat human infections. The fungus Candida tropicalis can switch to a haploid state (single copy of genes instead of two) when exposed to this agricultural chemical, and these altered cells become resistant to both agricultural and medical antifungal drugs. This explains how resistance that develops in agricultural settings can spread to clinical settings, creating a public health threat.

Background

Azole fungicides are widely used in agriculture and as antifungals in clinical settings. Candida tropicalis is an opportunistic fungal pathogen with high azole resistance and a mortality rate of 55-60% in invasive infections. Exposure to agricultural azoles can facilitate the emergence of clinical azole resistance in natural environments.

Objective

To investigate the mechanisms underlying acquired azole resistance in Candida tropicalis when exposed to tebuconazole, an agricultural fungicide. The study aims to determine how ploidy plasticity contributes to the emergence of drug-resistant strains with cross-resistance to clinical azoles.

Results

Tebuconazole induced ploidy shifts generating haploid, triploid, and aneuploid cells. Haploid cells exhibited resistance to both agricultural and clinical azoles and were mating-competent. Copy number variations in azole resistance genes TAC1 and ERG11 were identified, along with isochromosome formation potentially conferring drug resistance.

Conclusion

Ploidy plasticity, particularly the formation of haploid and mating-competent cells, drives azole resistance in C. tropicalis. The study suggests that isochromosome formation could be a general resistance mechanism triggered by agricultural and clinical azoles, with implications for understanding cross-resistance emergence.
  • Published in:PLoS Biology,
  • Study Type:Experimental Evolution Study,
  • Source: PMID: 40173118, DOI: 10.1371/journal.pbio.3003083
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