Pseudohyphal growth of the emerging pathogen Candida auris is triggered by genotoxic stress through the S phase checkpoint
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Abstract
Candida auris is a newly emerged fungal pathogen of humans. This species was first reported in 2009 when it was identified in an ear infection of a patient in Japan. However, despite intense interest in this organism as an often multidrug-resistant fungus, there is little knowledge about its cellular biology. During infection of human patients, fungi are able to change cell shape from ellipsoidal yeast cells to elongated filaments to adapt to various conditions within the host organism. There are different types of filaments, which are triggered by reactions to different cues. Candida auris fails to form filaments when exposed to triggers that stimulate yeast filament morphogenesis in other fungi. Here, we show that it does form filaments when its DNA is damaged. These conditions might arise when Candida auris cells interact with host immune cells or during growth in certain host tissues (kidney or bladder) or during treatment with antifungal drugs.
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Certain Candida species can transition from yeast forms to filamentous structures, producing true hyphae in species like C. albicans, C. dubliniensis, and C. tropicalis, or pseudohyphae in species such as C. auris and C. parapsilosis.
“Certain Candida species can transition from yeast forms to filamentous structures, producing true hyphae in species like C. albicans, C. dubliniensis, and C. tropicalis, or pseudohyphae in species such as C. auris and C. parapsilosis96–98.”
From Distinct echinocandin responses of Candida albicans and Candida auris cell walls revealed by solid-state NMR (2025) · cites this paper as [97]
The Results section on genes associated with hyphal growth identifies C. albicans, C. tropicalis, and C. dubliniensis as capable of forming true hyphae. The Results section on C. auris reports pseudohyphae under genotoxic stress. The paper says C. parapsilosis cannot form true hyphae, but does not say it forms pseudohyphae; it also notes that C. auris filamentation varies by strain. (LLM, conf=0.86)
Experimental — accuracy not yet measuredClinical isolates of C. auris can exhibit different morphotypes such as filamentous, pseudohyphal, and yeast forms.
“Clinical isolates of C. auris can exhibit different morphotypes such as filamentous, pseudohyphal, and yeast forms (8–14).”
From Yeast and filamentous <i>Candida auris</i> stimulate distinct immune responses in the skin (2024) · cites this paper as [14]
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Cites
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“triggers constitutive pseudohyphal growth in yeasts (49, 70, 71).”
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<i>Candida auris</i> Genetics and Emergence
Chowdhary, A., Jain, K., & Chauhan, N. (2023) · Annual Review of Microbiology · doi:10.1146/annurev-micro-032521-015858 · Cited by 158 · see citing works
Santana, D. J., & O’Meara, T. R. (2021) · Nature Communications · doi:10.1038/s41467-021-27545-5 · Cited by 91 · see citing works
Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection
Bing, J., Guan, Z., Zheng, T., Ennis, C. L., Nobile, C. J., Chen, C., Chu, H., & Huang, G. (2024) · Nature Communications · doi:10.1038/s41467-024-46786-8 · Cited by 74 · see citing works
Vila, T., Montelongo-Jauregui, D., Ahmed, H., Puthran, T., Sultan, A. S., & Jabra-Rizk, M. A. (2020) · mSphere · doi:10.1128/msphere.00760-20 · Cited by 58 · see citing works
Kim, J.-S., Lee, K.-T., Lee, M. H., Cheong, E., & Bahn, Y.-S. (2021) · mBio · doi:10.1128/mbio.02729-21 · Cited by 53 · see citing works
Dickwella Widanage, M. C., Singh, K., Li, J., Yarava, J. R., Scott, F. J., Xu, Y., Gow, N. A. R., Mentink-Vigier, F., Wang, P., Lamoth, F., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61678-1 · Cited by 51 · see citing works
Self-citationNative human and mouse skin infection models to study Candida auris-host interactions
Seiser, S., Arzani, H., Ayub, T., Phan-Canh, T., Staud, C., Worda, C., Kuchler, K., & Elbe-Bürger, A. (2024) · Microbes and Infection · doi:10.1016/j.micinf.2023.105234 · Cited by 29 · see citing works
Cha, H., Won, D., Kang, S., Kim, E.-S., Lee, K.-A., Lee, W.-J., Lee, K.-T., & Bahn, Y.-S. (2025) · PLOS Pathogens · doi:10.1371/journal.ppat.1013363 · Cited by 24 · see citing works
Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i>
Louvet, M., Li, J., Brandalise, D., Bachmann, D., Sala de Oyanguren, F., Labes, D., Jacquier, N., Genoud, C., Mucciolo, A., Coste, A. T., et al. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.01531-24 · Cited by 20 · see citing works
Cha, H., Won, D., & Bahn, Y.-S. (2025) · mBio · doi:10.1128/mbio.02475-23 · Cited by 19 · see citing works
Deng, Y., Xu, M., Li, S., Bing, J., Zheng, Q., Huang, G., Liao, W., Pan, W., & Tao, L. (2024) · PLOS Pathogens · doi:10.1371/journal.ppat.1012362 · Cited by 16 · see citing works
Yeast and filamentous <i>Candida auris</i> stimulate distinct immune responses in the skin
Bryak, G., Cox, A., Lionakis, M. S., & Thangamani, S. (2024) · mSphere · doi:10.1128/msphere.00055-24 · Cited by 13 · see citing works
“Clinical isolates of C. auris can exhibit different morphotypes such as filamentous, pseudohyphal, and yeast forms (8–14).”
Background
- Authors
- Bravo Ruiz, G., Ross, Z. K., Gow, N. A. R., & Lorenz, A.
- Affiliations
- Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
- University of Aberdeen (GB)
- University of Exeter (GB)
- Corresponding author
- Lorenz, Alexander
- Venue
- mSphere
- Publisher
- American Society for Microbiology
- Published
- 2020-04-29
- Volume
- 5
- Issue
- 2
- ISSN
- 2379-5042 (ISSN-L)
- PMC
- PMC7067593
- OpenAlex
- W3012011716
- Cited by
- 101
- References
- 7
- Citations by year
- 2026: 21 · 2025: 14 · 2024: 18 · 2023: 13 · 2022: 11 · 2021: 16 · 2020: 8
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mSphere (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Aberdeen University Research Archive (Aberdeen University) (acceptedVersion, cc-by-nd)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion, cc-by-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Open Research Exeter (University of Exeter) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (212524/Z/18/Z)
- UK Research and Innovation | Medical Research Council (MR/P501955/2, MR/N006364/2)
- 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, pseudohyphal growth, genotoxic stress, DNA damage, S-phase checkpoint, yeast-to-hypha transition, antifungal resistance, emerging fungal pathogens, host-pathogen interaction
- MeSH terms
- Adaptation, Physiological, Candida, DNA Damage, DNA, Fungal, Flucytosine, Hydroxyurea, Methyl Methanesulfonate, Mutagens, Virulence, Hyphae, Host-Pathogen Interactions, S Phase Cell Cycle Checkpoints
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