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Peer-reviewedCC BY-NC-NDFungal biology and biotechnology

Antifungal resistance landscapes in major fungal pathogens in Zhejiang, China.

  • Haochuan Wang1,2
  • Jinxiao Zhang3
  • Nan Zhang4
  • Youqi Ji5
  • Xin Hong6,7
  • Hugo Sámano-Sánchez1
  • Fan Xu4
  • Yi Han4
  • Xushen Xiong8
  • Susan C Welburn1,2
  • Holger Schulze2
  • Till T Bachmann9,10
2 more authors
  • Yumei Ge11,12,13,14
  • Daniel H Scharf15,16,17
17 affiliations
  1. 1Zhejiang University-University of Edinburgh Institute (ZJE), Zhejiang University School of Medicine, Zhejiang University, Haining, Zhejiang, China.
  2. 2Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK.
  3. 3The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
  4. 4Department of Microbiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  5. 5The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  6. 6Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
  7. 7Department of Green Pharmaceutical Collaborative Innovation Center, School of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
  8. 8The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  9. 9Zhejiang University-University of Edinburgh Institute (ZJE), Zhejiang University School of Medicine, Zhejiang University, Haining, Zhejiang, China. [email protected].
  10. 10Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK. [email protected].
  11. 11Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China. [email protected].
  12. 12Key Laboratory of Precision Medicine for Head and Neck Cancers of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China. [email protected].
  13. 13Department of Clinical Laboratory, Zhejiang Provincial People's Hospital Bijie Hospital, Bijie, Guizhou, China. [email protected].
  14. 14Key Laboratory for Cancer Prevention and Treatment of Guizhou Province, Bijie, Guizhou, China. [email protected].
  15. 15Zhejiang University-University of Edinburgh Institute (ZJE), Zhejiang University School of Medicine, Zhejiang University, Haining, Zhejiang, China. [email protected].
  16. 16The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China. [email protected].
  17. 17Department of Microbiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. [email protected].
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Abstract

Background

Invasive fungal infections caused by Aspergillus fumigatus and other pathogenic fungi represent a major global health threat, with treatment increasingly complicated by the emergence of antifungal drug resistance. Azole antifungals serve as the first-line therapy for aspergillosis, but resistance rates vary substantially across geographical regions. This study aimed to characterize the antifungal resistance landscape among clinical fungal isolates from Hangzhou and Yiwu cities in Zhejiang Province, Eastern China, and to elucidate the molecular mechanisms underlying azole resistance in Aspergillus fumigatus.Results

We analyzed 110 Aspergillus clinical isolates for antifungal susceptibility. Among A. fumigatus strains, 8.6% exhibited azole resistance, with half of these harboring the tandem repeat mutation TR34/L98H in the cyp51A gene. One resistant strain carried the TR46/Y121F/T289A mutation combination. Minimum inhibitory concentration testing revealed that 8.6% of A. fumigatus isolates were resistant to amphotericin B We identified one resistant isolate without known resistance mutations and characterized it through whole-genome sequencing and transcriptomic analysis. Novel mutations S437F in cyp51A and P298T in hmg1 were discovered; however, functional validation using CRISPR-Cas9 demonstrated these mutations do not directly confer resistance. Instead, transcriptomic profiling revealed significant upregulation of ergosterol biosynthesis pathway genes and efflux transporter genes, suggesting alternative resistance mechanisms. Among non-A. fumigatus species, all A. niger isolates displayed resistance to itraconazole and posaconazole.Conclusions

This comprehensive regional surveillance reveals concerning patterns of antifungal resistance among major human pathogenic fungi in Zhejiang Province, China. The identification of both classical resistance mutations and novel transcription-mediated resistance mechanisms highlights the complex and evolving nature of antifungal resistance. These findings emphasize the critical need for continued surveillance programs and rapid resistance detection methods to inform clinical treatment strategies and improve patient outcomes.

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Cite

BibTeXRIS
BibTeX
@article{wang2026antifungal,
  title = {{Antifungal resistance landscapes in major fungal pathogens in Zhejiang, China.}},
  author = {Haochuan Wang and Jinxiao Zhang and Nan Zhang and Youqi Ji and Xin Hong and Hugo Sámano-Sánchez and Fan Xu and Yi Han and Xushen Xiong and Susan C Welburn and Holger Schulze and Till T Bachmann and Yumei Ge and Daniel H Scharf},
  journal = {Fungal biology and biotechnology},
  year = {2026},
  month = oct,
  doi = {10.1186/s40694-026-00223-1},
  url = {https://europepmc.org/article/MED/42919349},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Antifungal resistance landscapes in major fungal pathogens in Zhejiang, China.
AU  - Haochuan Wang
AU  - Jinxiao Zhang
AU  - Nan Zhang
AU  - Youqi Ji
AU  - Xin Hong
AU  - Hugo Sámano-Sánchez
AU  - Fan Xu
AU  - Yi Han
AU  - Xushen Xiong
AU  - Susan C Welburn
AU  - Holger Schulze
AU  - Till T Bachmann
AU  - Yumei Ge
AU  - Daniel H Scharf
PY  - 2026
DA  - 2026/10/22
JO  - Fungal biology and biotechnology
DO  - 10.1186/s40694-026-00223-1
UR  - https://europepmc.org/article/MED/42919349
AB  - Background  Invasive fungal infections caused by Aspergillus fumigatus and other pathogenic fungi represent a major global health threat, with treatment increasingly complicated by the emergence of antifungal drug resistance. Azole antifungals serve as the first-line therapy for aspergillosis, but resistance rates vary substantially across geographical regions. This study aimed to characterize the antifungal resistance landscape among clinical fungal isolates from Hangzhou and Yiwu cities in Zhejiang Province, Eastern China, and to elucidate the molecular mechanisms underlying azole resistance in Aspergillus fumigatus.Results  We analyzed 110 Aspergillus clinical isolates for antifungal susceptibility. Among A. fumigatus strains, 8.6% exhibited azole resistance, with half of these harboring the tandem repeat mutation TR34/L98H in the cyp51A gene. One resistant strain carried the TR46/Y121F/T289A mutation combination. Minimum inhibitory concentration testing revealed that 8.6% of A. fumigatus isolates were resistant to amphotericin B We identified one resistant isolate without known resistance mutations and characterized it through whole-genome sequencing and transcriptomic analysis. Novel mutations S437F in cyp51A and P298T in hmg1 were discovered; however, functional validation using CRISPR-Cas9 demonstrated these mutations do not directly confer resistance. Instead, transcriptomic profiling revealed significant upregulation of ergosterol biosynthesis pathway genes and efflux transporter genes, suggesting alternative resistance mechanisms. Among non-A. fumigatus species, all A. niger isolates displayed resistance to itraconazole and posaconazole.Conclusions  This comprehensive regional surveillance reveals concerning patterns of antifungal resistance among major human pathogenic fungi in Zhejiang Province, China. The identification of both classical resistance mutations and novel transcription-mediated resistance mechanisms highlights the complex and evolving nature of antifungal resistance. These findings emphasize the critical need for continued surveillance programs and rapid resistance detection methods to inform clinical treatment strategies and improve patient outcomes.
SN  - 2054-3085
ER  -