A single gene mutation underpins metabolic adaptation and acquisition of filamentous competence in the emerging fungal pathogen Candida auris
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Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C 2 H 2 zinc finger transcription factor-encoding gene GFC1 (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid β-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1 Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection.
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Gfc1, the homolog of Candida albicans Bcr1, plays a critical regulatory role in hyphal formation and biofilm development in pathogenic Candida species.
“It has been known that the Gfc1 (the homolog of C. albicans Bcr1) transcription factor plays a critical regulatory role in hyphal formation and biofilm development in pathogenic Candida species29,47,48.”
From The Wor2 phenotypic switching regulator controls biofilm formation in Candida auris (2026) · cites this paper as [48]
The Discussion identifies C. albicans Bcr1 as Gfc1’s closest homolog, and the Results show that Gfc1 negatively regulates filamentous growth in C. auris. The Discussion attributes biofilm development to Bcr1 in C. albicans white cells, not to Gfc1, and does not establish Gfc1’s role across pathogenic Candida species. Page numbers were not available in our copy. (LLM, conf=0.88)
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Sofras, D., Carolus, H., Subotić, A., Romero, C. L., Ennis, C. L., Hernday, A. D., Nobile, C. J., Rybak, J. M., & Dijck, P. V. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.09.632232 · Cited by 1 · see citing works
The Wor2 phenotypic switching regulator controls biofilm formation in Candida auris
Liang, W., Guan, S., Bing, J., Du, H., Zheng, Q., Tao, L., Li, B., Huang, G., & Chu, H. (2026) · npj Biofilms and Microbiomes · doi:10.1038/s41522-026-01043-2
Self-citationOsama, D., Alsedawy, M., Hussein, M. S., Hassan, M. A., Elrefaey, S. M., & Tawfick, M. M. (2026) · Antonie van Leeuwenhoek · doi:10.1007/s10482-026-02393-9
Wei, M., Xue, Y., Mei, Y., Zhu, J., Li, L., Ma, X., Chen, G., & Zhu, M. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1860369
Ma, M., Xu, M., Guan, S., Fan, S., Huang, G., & Li, T. (2026) · Virulence · doi:10.1080/21505594.2026.2711487
Self-citationSoni, A., Vrzoňová, R., Paulovičová, L., Bzducha‐Wróbel, A., & Farkaš, P. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.154672
- Authors
- Deng, Y., Xu, M., Li, S., Bing, J., Zheng, Q., Huang, G., Liao, W., Pan, W., & Tao, L.
- Affiliations
- Second Military Medical University (CN)
- Fudan University (CN)
- Corresponding author
- Pan, Weihua
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2024-07-08
- Volume
- 20
- Issue
- 7
- Pages
- e1012362
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC11257696
- OpenAlex
- W4400408034
- Cited by
- 16
- References
- 82
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 1
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Update notices
- new_version (2024-07-18)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Program of China (2021YFC2300400)
- National Natural Science Foundation of China (32170194, 32370202, 31930005, 82272359, 82272355, 82072257, 82202546)
- Science and Technology Commission of Shanghai Municipality (20DZ2272000, 21410750500)
- Clinical Research Plan of SHDC (SHDC22022302)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida auris, filamentous growth, C2H2 zinc finger transcription factor, glycerol, fatty acid beta-oxidation, metabolic adaptation, skin colonization, multidrug resistance, fungal pathogen evolution, single-gene mutations
- MeSH terms
- Candida auris, Adaptation, Physiological, Animals, Candidiasis, Fungal Proteins, Glycerol, Humans, Mutation, Transcription Factors, Gene Expression Regulation, Fungal, Mice
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