Cited by 143Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index; none of the 45 sources its claims cite is checked for support yet.

A Candida auris –specific adhesin, Scf1 , governs surface association, colonization, and virulence

Open access

Abstract

Candida auris is an emerging fungal pathogen responsible for health care–associated outbreaks that arise from persistent surface and skin colonization. We characterized the arsenal of adhesins used by C. auris and discovered an uncharacterized adhesin, Surface Colonization Factor (Scf1), and a conserved adhesin, Iff4109, that are essential for the colonization of inert surfaces and mammalian hosts. SCF1 is apparently specific to C. auris , and its expression mediates adhesion to inert and biological surfaces across isolates from all five clades. Unlike canonical fungal adhesins, which function through hydrophobic interactions, Scf1 relies on exposed cationic residues for surface association. SCF1 is required for C. auris biofilm formation, skin colonization, virulence in systemic infection, and colonization of inserted medical devices.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

The paper identifies Scf1 (SCF1; B9J08_001458), a *Candida auris*–specific adhesin, and the conserved adhesin IFF4109 as key mediators of surface attachment, colonization, biofilm formation, and virulence. Scf1 promotes adhesion via exposed cationic residues rather than canonical hydrophobic interactions, and its expression varies across *C. auris* isolates in a manner correlated with adhesive capacity.

Key findings

  • Of twelve *C. auris* ALS/IFF-HYR adhesin deletion mutants tested, only deletion of IFF4109 (B9J08_004109) caused an adhesive defect; a screen of 2,560 insertional mutants found the greatest adhesion loss in tnSWI1 (B9J08_003460) and tnBCY1 (B9J08_002818), with SCF1 (B9J08_001458) as the strongest dysregulated gene in tnSWI1.
  • SCF1 is apparently specific to *C. auris* and *C. haemulonii*. Across 23 *C. auris* isolates from all five clades, adhesion varied significantly (p=2×10⁻¹⁶, F=35.06, one-way ANOVA), whereas 19 diverse *C. albicans* isolates showed no significant adhesive variation (p=0.054, F=1.856). SCF1 transcript abundance correlated with adhesion (r=0.87, p=8.4×10⁻⁸), while IFF4109 did not (r=0.3, p=0.25).
  • Scf1-mediated adhesion does not depend on cell surface hydrophobicity: IFF4109 deletion reduced hydrophobicity, but SCF1 deletion or overexpression did not. Only SCF1 mediated adhesion to a hydrophilic, vacuum plasma–treated polystyrene surface. High arginine concentrations ablated AR0382 adhesion, and the HHRR cationic-aromatic cluster at residues 52–55 was required for adhesion; a wild-type Scf1 peptide (residues 50–62) bound polystyrene microspheres, while mutation of HHRR ablated binding.
  • SCF1 and IFF4109 were functionally redundant for biofilm formation, but loss of both ablated AR0382 biofilm and rat central venous catheter colonization; SCF1 overexpression potentiated AR0387 colonization. Loss of both adhesins reduced human skin explant and murine skin colonization and reduced dissemination to kidneys and heart. In disseminated infection, wild-type AR0382 caused 100% mortality within 12 days versus 20% mortality after 21 days for the mutant; SCF1 overexpression reduced median survival of AR0387-infected mice from 18.5 days to 11.5 days.

Methods

  • Genetic and phenotypic assays in *C. auris* clade I AR0382: individual deletion mutants for twelve ALS/IFF-HYR adhesin genes, a 2,560-member insertional mutant library screen, flow cytometric adhesion assays to polystyrene microspheres, RNA-seq, complementation, epitope tagging, overexpression, AlphaFold2 modeling, peptide binding assays, MATH hydrophobicity assays, and biofilm assays.
  • Isolate panel and expression analysis: adhesion measured for 23 *C. auris* isolates representing all five clades and 19 genetically diverse *C. albicans* clinical isolates; SCF1 and IFF4109 transcript abundance compared with adhesion.
  • In vivo and ex vivo colonization/infection models: polyethylene rat central venous catheters, ex vivo human skin explants, in vivo murine skin, and immunosuppressed mice infected intravenously with 5×10⁷ *C. auris* cells; histopathology at 7 days and survival monitored for 21 days. Statistical tests included one-way ANOVA with post-hoc tests, Student’s t-test, Pearson correlation, and Mantel-Haenszel log-rank test with Benjamini-Hochberg correction.

Limitations

  • Stated in the paper: the mechanisms by which SCF1 and IFF4109 interact with host systems remain unclear; the selective pressure governing differential SCF1 expression is unknown; and whether the lack of surface-association phenotypes for other conserved adhesin genes reflects functional or regulatory divergence remains to be explored.
  • Evident from the text: many mechanistic and virulence experiments focus on the clade I AR0382 background and selected comparator isolates, so generalizability across all *C. auris* lineages is not fully established. The paper also relies on in vitro adhesion/biofilm assays and animal or ex vivo models, which may not fully recapitulate human colonization and infection. No dedicated limitations section is present in the provided text.

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Integrity signals

Registry

Crossref · 10.1126/science.adf8972

Cites

79 of 79 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

64 Own result · 26 Sources not found · 12 Own interpretation · 2 No basis given

Show all 57 claims

  • It may state two separate claims as one. 34
  • Probably not a substantial claim. 18
47 of 47
  • The paper relies on this without support.

    Colonization requires the initial physical association and attachment between fungal cells and substrate.

    “Colonization requires the initial physical association and attachment between fungal cells and substrate.”
  • The paper relies on this without support.

    Adhesion to polymer substrates is a valid model for surface association and colonization.

    “we measured the adhesion between fungal cells and polymer substrates as a model for surface association.”
  • The paper relies on this without support.

    Murine and ex vivo human skin models reflect clinically relevant colonization and disseminated infection in humans.

    “we also investigated the importance of these adhesins in disseminated infection.”
  • The paper relies on this without support.

    AlphaFold2 structural predictions reflect the actual structure and adhesive behavior of Scf1.

    “we examined the apical N-terminal domain using AlphaFold2, which suggested this domain contains a core Fibronectin-type III fold similar to the FLO11 family of adhesins characterized in Saccharomyces cerevisiae and conserved throughout Ascomycota (Fig. S8A) (32,35).”
4 of 4

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Metadata

Authors
Santana, D. J., Anku, J. A. E., Zhao, G., Zarnowski, R., Johnson, C. J., Hautau, H., Visser, N. D., Ibrahim, A. S., Andes, D., Nett, J. E., Singh, S., & O’Meara, T. R.
Affiliations
  • University of Michigan (US)
  • University of Ghana (GH)
  • Department of Medicine, University of Wisconsin, Madison, WI, USA.
  • University of Wisconsin–Madison (US)
  • University of California, Los Angeles (US)
Corresponding author
O’Meara, Teresa R.
Venue
Science
Published
2023-09-29
Volume
381
Issue
6665
Pages
1461-1467
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W4387128705
Cited by
142
References
76
Citations by year
2026: 65 · 2025: 40 · 2024: 34 · 2023: 3
FWCI
26.50
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • PubMed Central (submittedVersion)
Funders
  • American Heart Association (938451)
  • National Institutes of Health (5t32ai007413-32, T32 AI00,7413, R21AI159583, R01AI073289, T32AI007528, R01AI145939, KL2TR001882)
  • Japan Atomic Energy Agency
  • National Institute of Allergy and Infectious Diseases (T32-AI-007413, R01-AI073289, R21 AI159583, T32-AI007528, F31AI169823, R01 AI145939, R01AI141202, R01 AI063503, R21 AI169186)
  • National Center for Advancing Translational Sciences (KL2TR001882)
  • Clinical and Translational Science Institute, University of California, Los Angeles (KL2TR001882)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
Keywords
Candida auris, fungal adhesins, surface colonization, biofilm formation, virulence, skin colonization, medical device colonization, cationic residues, fungal adhesion, emerging fungal pathogens
MeSH terms
Protein Domains, Candida auris, Animals, Fungal Proteins, Humans, Microfilament Proteins, Virulence, Mice, Hydrophobic and Hydrophilic Interactions, Candidiasis, Invasive

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