Dynamic expression of candidalysin facilitates oral colonization of Candida albicans in mice
Candida albicans is a common fungal member of the human microbiota but can also cause infections via expression of virulence factors associated with the yeast-to-hyphae transition. The evolutionary selection pressure to retain these pathogenic traits for a commensal microorganism remains unclear. Here we show that filamentation and hyphae-associated factors, including the toxin candidalysin, are crucial for colonization of the oral cavity, a major reservoir of C. albicans. Low-virulent strains of C. albicans expressed the candidalysin-encoding gene ECE1 transiently upon exposure to keratinocytes in vitro. In mice, ECE1 mutants were defective at accessing terminally differentiated oral epithelial layers where the fungus is protected from IL-17-mediated immune defence. Tight regulation of ECE1 expression prevented detrimental effects of candidalysin on the host. Our results suggest that hyphae-associated factors such as candidalysin govern not only pathogenicity, but also mucosal colonization through direct host interactions enabling C. albicans to create and maintain its niche in the oral mucosa.
Authors
- Ricardo Fróis-Martins (ORCID: https://orcid.org/0000-0002-7338-2383)
- Selene Mogavero (ORCID: https://orcid.org/0000-0003-0642-0068)
- Bernhard Hube (ORCID: https://orcid.org/0000-0002-6028-0425)
- Natacha Sertour
- Julia Lagler
- Osama Elshafee
- Salomé LeibundGut‐Landmann (ORCID: https://orcid.org/0000-0002-5724-4837)
- Dominique Sanglard (ORCID: https://orcid.org/0000-0002-5244-4178)
- Sarah Mertens
- Kontxi Martinez de San Vicente (ORCID: https://orcid.org/0000-0003-3320-7035)
- Sophie Bachellier‐Bassi (ORCID: https://orcid.org/0000-0003-3970-4825)
- Christophe d’Enfert (ORCID: https://orcid.org/0000-0002-6235-3886)
- Tim B Schille (ORCID: https://orcid.org/0009-0008-8296-5434)
- Michelle Stokmaier
- Iman Kilb
Institutions
- Institut Pasteur (FR)
- University of Zurich (CH)
- Université Paris Cité (FR)
- University of Exeter (GB)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Friedrich Schiller University Jena (DE)
- University of Lausanne (CH)
Publication Details
- Journal
- Nature Microbiology
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1038/s41564-025-02122-4
- Citations
- 2
- Primary Topic
- Antifungal resistance and susceptibility
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- National Science Foundation
- Novartis Foundation
- European Commission
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Novartis Stiftung für Medizinisch-Biologische Forschung
- Uniscientia Foundation