In vitro exposure to the agricultural triazole tebuconazole selects for fluconazole cross-resistance and echinocandin tolerance in Candidozyma auris.

Authors

Lihao Peng, Yi Xu, Xinyi Chen, Wenhui Li, Liangsheng Guo

Published in

Frontiers in cellular and infection microbiology. Volume 16. Pages 1860421. Epub Jul 20, 2026.

Abstract

The agricultural triazole fungicide tebuconazole (TCZ) has been implicated in the emergence of azole resistance in human fungal pathogens, but its direct role in selecting resistance and tolerance in Candidozyma auris remains unclear. Here, we investigated whether laboratory exposure of a clade III clinical C. auris isolate to TCZ could induce cross-resistance to clinical antifungals. Among 17 agrochemicals tested, only TCZ exhibited intrinsic antifungal activity. Brief (48 h) exposure to sub-MIC TCZ (1 μg/mL) selected variants (6.9% frequency) with cross-resistance to TCZ and fluconazole, but full susceptibility to caspofungin. Exposure to supra-MIC TCZ (8-32 μg/mL) produced three phenotypic classes: Class 2 (TCZ-R, fluconazole-R) and Class 3 (TCZ-R, fluconazole-R, plus tolerance to caspofungin and micafungin). The frequency of Class 3 increased dose-dependently from 23% to 50% as TCZ concentration rose. RNA-Seq revealed that both classes overexpressed MDR1, TAC1b, UPC2 and FKS1, but Class 2 showed broad ergosterol pathway upregulation, whereas Class 3 exhibited restricted ergosterol activation but downregulation of the sole chitinase gene CHT1 (5.17-fold), a known mechanism of echinocandin tolerance. Unlike the CRS-MIS phenomenon in Candida glabrata, our Class 3 adaptors displayed equal tolerance to both caspofungin and micafungin. Collectively, these findings demonstrate that, in a clade III clinical isolate of C. auris under the tested laboratory conditions, laboratory exposure to an agricultural triazole can rapidly select for clinically relevant azole cross-resistance and echinocandin tolerance in C. auris, suggesting that environmental fungicide use may inadvertently compromise the efficacy of last-line antifungals.

PMID:
42548818
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

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