A recent study published in PLOS Biology highlights the growing concern over Candida tropicalis, a human fungal pathogen that has become increasingly resistant to azoles, a class of antifungal drugs commonly used in clinical settings. C tropicalis is an obligate diploid organism with an incomplete and atypical sexual cycle, and recent years have seen a surge in azole-resistant strains worldwide.
This study explores the impact of tebuconazole (TBZ), an agricultural triazole fungicide, on C tropicalis. The results reveal that exposure to TBZ induces ploidy plasticity in C tropicalis, leading to the formation of haploid cells. These ploidy-altered strains show cross-resistance to TBZ and several clinical azoles, including fluconazole and voriconazole. Despite their slower growth in vitro and reduced virulence in a mouse model of systemic infection compared to diploid cells, the haploid C tropicalis cells retain the ability to undergo key processes such as filamentation, white-opaque switching, and mating.
Moreover, flow cytometry analysis of a clinical strain with low genome heterozygosity has shown that natural haploid cells of C tropicalis exist in nature. While auto-diploidization, the process by which haploid cells spontaneously switch back to the diploid form was observed, the investigators noted that this transition does not fully restore the fitness of the haploid cells, possibly due to the loss of some genes or heterozygosity.
In their discussion, the investigators emphasized the role of environmental azoles in promoting the evolution of antifungal resistance. “Azoles are widely used not only for antifungal therapy in clinical settings but also for crop protection and timber preservation in agricultural settings,” the authors explained. “The environmental application and accumulation of azoles could promote the evolution of antifungal resistance in these species in nature.”
The study also underlines that while ploidy alterations in C tropicalis are significant, the exact mechanisms behind the formation of haploid cells in pathogenic species and the advantages they may provide over diploid cells remain unclear. This gap in knowledge underscores the need for further research into the genetic factors that influence ploidy transitions in fungi exposed to environmental azoles.
What You Need To Know
Exposure to the agricultural fungicide TBZ induces ploidy plasticity in C tropicalis, leading to the formation of haploid cells that show cross-resistance to both agricultural and clinical azoles.
Haploid C tropicalis cells can undergo critical biological processes but exhibit slower growth and reduced virulence compared to diploid cells.
The study highlights that environmental exposure to azole fungicides in agricultural settings may contribute to the development of azole-resistant C tropicalis strains, posing a risk for human health and agricultural systems.
Similarly, a study published in the CDC’s Emerging Infectious Diseases journal in November 2024 explored the detection of fluconazole-resistant C tropicalis in orchards in Taiwan. The study found that agricultural environments could serve as a reservoir for azole-resistant strains of C tropicalis, with fluconazole resistance correlating with resistance to several agricultural fungicides, including tebuconazole. Notably, the researchers observed that a particular C tropicalis genotype (clade 4) exhibited resistance to fluconazole and cross-resistance to agricultural azoles. This finding aligns with the current study, further supporting the link between agricultural fungicide use and the rise of drug-resistant fungal strains that pose risks to human health.
These findings underscore the importance of understanding the role of agricultural fungicides in the emergence of antifungal resistance. The genetic mechanisms driving resistance, such as mutations in the ERG11 gene, are consistent with the observations in the current study that ploidy alterations might contribute to the adaptive capacity of C tropicalis to environmental pressures, including exposure to fungicides.
The studies highlight the critical need for careful management of azole fungicides in clinical and agricultural settings to mitigate the emergence of drug-resistant fungal pathogens. The discovery of haploid cells in C tropicalis not only advances our understanding of its genetic plasticity but also opens the door to the development of novel genetic tools for fungal research, with potential applications in combating antifungal resistance.
References
1. Hu T, Zheng Q, Cao C, Li S, Huang Y, Guan Z, et al. (2025) An agricultural triazole induces genomic instability and haploid cell formation in the human fungal pathogen Candida tropicalis . PLoS Biol 23(4): e3003062. https://doi.org/10.1371/journal.pbio.3003062
2. Tseng K, Chen Y, Zhou Z, et al. Detection in Orchards of Predominant Azole-Resistant Candida tropicalis Genotype Causing Human Candidemia, Taiwan. Emerging Infectious Diseases. 2024;30(11):2323-2332. doi:10.3201/eid3011.240545
