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

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

Open access
Santana, Darian J., Anku, Juliet A. E., Zhao, Guolei, Zarnowski, Robert, Johnson, Chad J., Hautau, Haley, Visser, Noelle D., Ibrahim, Ashraf S. +4 more·2023·Science
DOI 10.1126/science.adf8972PMC PMC11235122
Open this paper in CoChat — free accountOpen PDF

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.

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.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1126/science.adf8972

Cites

79 of 79 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 45 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    The nonspecific surface association driven by SCF1 does not occur through canonical hydrophobic interactions, but rather through cation-substrate interactions.

    “The nonspecific surface association driven by SCF1 does not occur through canonical hydrophobic interactions, but rather through cation-substrate interactions.”
    Quote in the paperNot a substantial claim
  • Findingown data

    SCF1 is critical for robust colonization of in vivo central venous catheters.

    “SCF1 is critical for biofilm formation in vitro, robust colonization of in vivo central venous catheters, colonization of both human and murine skin, and virulence in disseminated infection.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Murine and ex vivo human skin models reflect clinically relevant colonization and disseminated infection in humans.
  • Findingown data

    Complementation with an epitope-tagged SCF1 allele in the endogenous locus rescued the adhesive defect.

    “Complementation with an epitope-tagged SCF1 allele in the endogenous locus rescued the adhesive defect, and the epitope-tagged Scf1 protein localized to the cell surface, consistent with its role as an adhesin (Fig. 1F, Fig. 1G).”
    Quote in the paperSubstantial claim
  • Findingown data

    19 genetically diverse C. albicans clinical isolates showed no significant adhesive variation (p=0.054, F=1.856, one-way ANOVA).

    “In contrast, a similar analysis of 19 genetically diverse C. albicans clinical isolates showed no significant adhesive variation (p=0.054,F=1.856, one-way ANOVA), indicating the surface association strategies of C. auris are more plastic than C. albicans (Fig. 2C).”
    Quote in the paperSubstantial claim
  • Findingown data

    The phenotypic plasticity in substrate association among C. auris isolates is tightly correlated with strain-specific transcriptional control of SCF1.

    “C. auris isolates from diverse and similar genetic lineages exhibit striking divergence in terms of substrate association, and this phenotypic plasticity is tightly correlated with strain-specific transcriptional control of SCF1.”
    Quote in the paperSubstantial claim
  • May combine two claims. 34
  • Classified as probably not a substantial claim. 18

  • May combine two claims.

    Findingown data

    Deletion of IFF4109 in the Δscf1 background did not significantly reduce attachment beyond deletion of SCF1 alone, suggesting non-additive roles for these adhesins.

    “Notably, deletion of IFF4109 in the Δscf1 background did not significantly reduce attachment beyond deletion of SCF1 alone, suggesting non-additive roles for these adhesins (Fig. 1F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The B9J08_001458 gene was also strongly downregulated in the tnBCY1 mutant while IFF4109 was not.

    “Notably, this same gene was also strongly downregulated in the tnBCY1 mutant while IFF4109 was not (Fig. S2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    SCF1 is encoded in a genomic locus in C. auris and C. haemulonii that is syntenic, lacking an SCF1 homolog, even to distantly related species.

    “SCF1 is encoded in a genomic locus in C. auris and C. haemulonii that is syntenic, lacking an SCF1 homolog, even to distantly related species (Fig. 2A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The strongest, most significantly dysregulated gene in tnSWI1 was an uncharacterized ORF (B9J08_001458), which had no significant primary sequence homology to characterized genes.

    “The strongest, most significantly dysregulated gene in tnSWI1 was an uncharacterized ORF (B9J08_001458), which had no significant primary sequence homology to characterized genes (Fig. 1D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SCF1 is necessary and sufficient for robust attachment of C. auris cells to polymer substrates.

    “SCF1 is necessary and sufficient for robust attachment of C. auris cells to polymer substrates.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Adhesion to polymer substrates is a valid model for surface association and colonization.

  • May combine two claims.

    Findingown data

    Although the C. haemulonii SCF1 homolog functionally complements Δscf1 in C. auris, it is not essential for adhesion in C. haemulonii and shows poor expression across isolates, indicating reliance on SCF1 for adhesion is specific to C. auris.

    “Although the C. haemulonii SCF1 homolog functionally complements Δscf1 in C. auris, it is not essential for adhesion in C. haemulonii and shows poor expression across isolates, indicating reliance on SCF1 for adhesion is specific to C. auris (Fig. S4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Of the twelve adhesin mutants, only deletion of IFF4109 conferred an adhesive defect, while still failing to completely ablate attachment.

    “Of the twelve adhesin mutants, only deletion of IFF4109 (B9J08_004109) conferred an adhesive defect, while still failing to completely ablate attachment (Fig. 1A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    IFF4892 encodes the entire canonical adhesin architecture and shows similar expression to IFF4109, but of the two, only IFF4109 is required for adhesion, suggesting individual adhesins mediate specific adhesive mechanisms.

    “However, IFF4892 encodes the entire canonical adhesin architecture and shows similar expression to IFF4109, but of the two, only IFF4109 is required for adhesion, suggesting individual adhesins mediate specific adhesive mechanisms (Fig. 1A, Fig. S3B) (25).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingcitation

    Increased flocculation and aggregation are associated with overexpression of ALS4112, while these phenotypes are not associated with SCF1, despite its transcriptional expression being among the highest 2.5% of all genes in this strain background.

    “Such functional specificity is shown by increased flocculation and aggregation associated with overexpression of ALS4112, while these phenotypes are not associated with SCF1, despite its transcriptional expression being among the highest 2.5% of all genes in this strain background (Fig. S3B, Fig. S3C, Fig. S3D) (30,31).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [30]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [31]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data

    Both IFF4109 and SCF1 mediated adhesion to the hydrophobic substrate.

    “Both IFF4109 and SCF1 mediated adhesion to the hydrophobic substrate (Fig. 3C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Several mutations had no adhesive impact, but an R54A R55A mutant exhibited a modest adhesive defect, while showing no discernable effect on SCF1 transcription, protein expression, or localization.

    “Several mutations had no adhesive impact, but an R54A R55A mutant exhibited a modest adhesive defect, while showing no discernable effect on SCF1 transcription, protein expression, or localization (Fig. S10).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Overexpression of SCF1 reduced the median survival of mice infected with AR0387 from 18.5 days to 11.5 days and ablated the difference in overall survival between the less virulent AR0387 and the more virulent AR0382.

    “Similarly, overexpression of SCF1 reduced the median survival of mice infected with AR0387 from 18.5 days to 11.5 days and ablated the difference in overall survival between the less virulent AR0387 and the more virulent AR0382 (Fig. 5G).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Murine and ex vivo human skin models reflect clinically relevant colonization and disseminated infection in humans.

  • May combine two claims.

    Findingown data

    In AR0382 and AR0387, the SCF1 locus is invariant, but other isolates exhibit allelic variation primarily concentrated in the low complexity tandem repeats.

    “In AR0382 and AR0387, the SCF1 locus is invariant, but other isolates exhibit allelic variation in, primarily concentrated in the low complexity tandem repeats (Table S1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The two adhesins were functionally redundant, and deletion of both was required to ablate biofilm formation in AR0382, suggesting the partial adhesive contributions of each is sufficient to establish colonization.

    “The two adhesins were functionally redundant, and deletion of both was required to ablate biofilm formation in AR0382, suggesting the partial adhesive contributions of each is sufficient to establish colonization (Fig. S13A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    SCF1 does not exhibit significant primary sequence homology to S. cerevisiae FLO11 and lacks conservation of the canonical aromatic bands responsible for adhesive functions in true FLO11 homologs.

    “However, SCF1 does not exhibit significant primary sequence homology to S. cerevisiae FLO11 and lacks conservation of the canonical aromatic bands responsible for adhesive functions in true FLO11 homologs (Fig. S8A, Fig. S8B) (32,35).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [32]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [35]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data

    The wild type Scf1 peptide was similarly able to adhere to phosphotidylcholine microparticles, and SCF1 expression potentiated lipid particle binding by C. auris cells, suggesting SCF1 may also contribute to association with biotic substrates.

    “The wild type Scf1 peptide was similarly able to adhere to phosphotidylcholine microparticles, and SCF1 expression potentiated lipid particle binding by C. auris cells, suggesting SCF1 may also contribute to association with biotic substrates (Fig. S12).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The magnitude of overexpression using the TEF1 promoter (approximately 2^8-fold increase) was similar to and did not exceed the naturally varying magnitude of expression difference between the two wild type isolates AR0382 and AR0387 (approximately 2^9-fold change).

    “Importantly, the magnitude of overexpression using the TEF1 promoter (approximately 2 8 -fold increase) was similar to and did not exceed the naturally varying magnitude of expression difference between the two wild type isolates AR0382 and AR0387 (approximately 2 9 -fold change) (Fig. 2D, Fig. 2E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Loss of SCF1 and IFF4109 substantially attenuated the virulence of AR0382, with the wild type causing 100% mortality within 12 days of infection and the mutant causing 20% mortality after 21 days.

    “Loss of SCF1 and IFF4109 substantially attenuated the virulence of AR0382, with the wild type causing 100% mortality within 12 days of infection and the mutant causing 20% mortality after 21 days (Fig. 5G).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Murine and ex vivo human skin models reflect clinically relevant colonization and disseminated infection in humans.

  • May combine two claims.

    Findingcitation

    Similar concentrations of NaCl or other non-cationic amino acids did not produce the same effect, while exogenous lysine produced a more modest inhibition of attachment, consistent with lysine's weaker ability to form electrostatic interactions.

    “Similar concentrations of NaCl or other non-cationic amino acids did not produce the same effect, while exogenous lysine produced a more modest inhibition of attachment, consistent with lysine's weaker ability to form electrostatic interactions (Fig. 4B) (41).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data

    The wild-type Scf1 peptide adhered to polystyrene microspheres, but mutation of the HHRR cluster completely ablated this ability.

    “The wild-type peptide adhered to polystyrene microspheres, but mutation of the HHRR cluster completely ablated this ability (Fig. 4E, Fig. 4F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    AR0382 and AR0387 still exhibited differential adhesion to the hydrophilic surface, indicating hydrophobic interactions are not primarily responsible for the differential strain phenotypes.

    “Notably, AR0382 and AR0387 still exhibited differential adhesion to the hydrophilic surface, indicating hydrophobic interactions are not primarily responsible for the differential strain phenotypes (Fig. 3D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Deletion of the IFF4109 adhesin in AR0382 reduced cell surface hydrophobicity, which was rescued to wild type levels by complementation.

    “Deletion of the IFF4109 adhesin in AR0382 reduced cell surface hydrophobicity, which was rescued to wild type levels by complementation (Fig. 3A, Fig. 3B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Only SCF1 mediated adhesion to the hydrophilic substrate, showing that SCF1 is not dependent on hydrophobicity.

    “However, only SCF1 mediated adhesion to the hydrophilic substrate, showing that SCF1 is not dependent on hydrophobicity (Fig. 3D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Loss of one adhesin did not result in dysregulation of the other, suggesting the interaction is not a regulatory one.

    “Loss of one adhesin did not result in dysregulation of the other, suggesting the interaction is not a regulatory one (Fig. S7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SCF1 mediates host colonization and infection phenotypes.

    “SCF1 mediates host colonization and infection phenotypes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    IFF4109, but not SCF1, mediates adhesion through cell surface hydrophobicity.

    “IFF4109, but not SCF1, mediates adhesion through cell surface hydrophobicity.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Loss of ALS1 alone reduces Candida albicans adhesion, despite the presence of seven other ALS genes.

    “For instance, loss of ALS1 alone reduces Candida albicans adhesion, despite the presence of seven other ALS genes (Fig. S3A) (29).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In Candida species, genetic expansion has resulted in the formation of adhesin families containing genes similar in sequence and domain architecture, with adhesive functions that are redundant or specific across family members.

    “In Candida species, genetic expansion has resulted in the formation of adhesin families containing genes similar in sequence and domain architecture, with adhesive functions that are redundant or specific across family members (23,24).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [23]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [24]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    C. auris encodes genes similar to members of the conserved ALS and IFF/HYR adhesin families found across the genus, although these genes may have expanded independently in C. auris and lack clear one-to-one homology with adhesins from well-characterized species.

    “C. auris encodes genes similar to members of the conserved ALS and IFF/HYR adhesin families found across the genus, although these genes may have expanded independently in C. auris and lack clear one-to-one homology with adhesins from well-characterized species.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (24)(25)(26)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    C. auris outbreaks are characterized by persistent colonization of patient skin and abiotic surfaces, which can remain positive for extensive periods and serve as a source of contaminative transmission.

    “C. auris outbreaks are characterized by persistent colonization of patient skin and abiotic surfaces, which can remain positive for extensive periods and serve as a source of contaminative transmission (8)(9)(10)(11)(12)(13)(14).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (8)(9)(10)(11)(12)(13)(14)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    For fungal pathogens, attachment is largely mediated by cell surface-exposed adhesin proteins.

    “For fungal pathogens, attachment is largely mediated by cell surface-exposed adhesin proteins (22).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    C. auris colonizes indwelling medical devices, which act as a risk factor for the development of invasive disease.

    “C. auris also colonizes indwelling medical devices, which act as a risk factor for the development of invasive disease (15)(16)(17)(18)(19)(20)(21).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (15)(16)(17)(18)(19)(20)(21)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    For bivalve, barnacle, and Vibrio organisms, cation-dependent surface interactions promote adhesion in aqueous and highly ionic environments.

    “For these organisms, cation-dependent surface interactions promote adhesion in aqueous and highly ionic environments (36-39).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [36]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [37]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [38]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [39]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Mediation of hydrophobic interactions is largely conserved among fungal adhesins, consistent with the adhesive mechanism of the conserved IFF4109.

    “Mediation of hydrophobic interactions is largely conserved among fungal adhesins, consistent with the adhesive mechanism of the conserved IFF4109 (32)(33)(34).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (32)(33)(34)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Prior work suggests vaccination or monoclonal antibody therapy targeting Als or Iff/Hyr adhesins may offer protection against lethal C. auris infection.

    “Prior work suggests vaccination or monoclonal antibody therapy targeting Als or Iff/Hyr adhesins may offer protection against lethal C. auris infection (27,47).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [47]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    Sequence variation between these two SCF1 alleles does not intrinsically contribute to functional differences in adhesion, and other factors may also influence adhesive capacity.

    “These findings show that sequence variation between these two SCF1 alleles does not intrinsically contribute to functional differences in adhesion, and that other factors may also influence adhesive capacity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Widespread differential regulation of SCF1 was observed among C. auris isolates regardless of clade, suggesting transcriptional control of this adhesin has adapted more recently than clade separation.

    “Notably, we observed widespread differential regulation of SCF1 among C. auris isolates regardless of clade, suggesting transcriptional control of this adhesin has adapted more recently than clade separation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Similar patterns of cation-aromatic clusters are also abundant in some lipid-binding proteins.

    “Interestingly, similar patterns of cation-aromatic clusters are also abundant in some lipid-binding proteins (40,43).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [40]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [43]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Elevated cell surface hydrophobicity promotes affinity for hydrophobic substrates.

    “Elevated cell surface hydrophobicity likewise promotes affinity for hydrophobic substrates (33).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    Adhesive systems in many marine organisms rely on similarly cation-rich proteins, which act through displacement of hydrated ions at the surface-liquid interface or direct cation-π interactions with substrates.

    “Adhesive systems in many marine organisms rely on similarly cation-rich proteins, which act through displacement of hydrated ions at the surface-liquid interface or direct cation-π interactions with substrates (36-40).”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [36]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [37]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [38]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [39]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [40]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    For other Candida species, adhesion to abiotic substrates is often nonspecific, with adhesins promoting affinity for hydrophobic substrates.

    “For other Candida species, adhesion to abiotic substrates is often nonspecific, with adhesins promoting affinity for hydrophobic substrates (32)(33)(34).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (32)(33)(34)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    C. auris encodes genes similar to the conserved ALS and IFF/HYR adhesin families, and proposed models suggest differential utilization of these adhesins may contribute to epidemiological differences among isolates.

    “C. auris encodes genes similar to the conserved ALS and IFF/HYR adhesin families, and proposed models suggest differential utilization of these adhesins may contribute to epidemiological differences among isolates (25, 27).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [25]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [27]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Biofilm growth can promote prolonged environmental persistence.

    “We measured the importance of these adhesins for biofilm growth, which can promote prolonged environmental persistence (11,(44)(45)(46).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (11,(44)(45)(46)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    The C. auris-specific adhesin SCF1 and the conserved adhesin IFF4109 are the principal mediators of association with abiotic surfaces, and additionally contribute substantially to infection and long-term colonization of both biological and abiotic surfaces.

    “Our findings suggest the C. aurisspecific adhesin SCF1 and the conserved adhesin IFF4109 are the principal mediators of association with abiotic surfaces, and additionally contribute substantially to infection and long-term colonization of both biological and abiotic surfaces.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Differential utilization of SCF1 by different isolates suggests an unknown selective pressure may govern its expression.

    “Still, differential utilization of SCF1 by different isolates suggests an unknown selective pressure may govern its expression.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    This ecological niche may have conferred similar selective pressures on adhesion mechanisms.

    “C. auris has been isolated from the coastal wetlands of the Andaman Islands and from a Colombian estuary, suggesting a possible marine natural habitat, and this ecological niche may have conferred similar selective pressures on adhesion mechanisms (48,49).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [49]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    C. auris has been isolated from the coastal wetlands of the Andaman Islands and from a Colombian estuary, suggesting a possible marine natural habitat.

    “C. auris has been isolated from the coastal wetlands of the Andaman Islands and from a Colombian estuary, suggesting a possible marine natural habitat, and this ecological niche may have conferred similar selective pressures on adhesion mechanisms (48,49).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [49]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Only 3 ALS genes have been identified in C. auris, unlike C. albicans which contains at least 11 Als adhesins.

    “unlike C. albicans, which contains at least 11 Als adhesins, thus far only 3 ALS genes have been identified in C. auris (20, 22).”

    From The <i>Candida auris</i> Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence (2024) · cites this paper as [22]

    In “Polymer surface attachment by the adhesin SCF1” (page unavailable), the paper describes C. albicans as having ALS1 and seven other ALS genes—eight, rather than the claimed at least eleven. It does not give a count of three ALS genes for C. auris; its count of twelve combines homologs of the ALS and IFF/HYR families. (LLM, conf=0.85)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • The cell wall adhesin Als4 plays a central role in biofilm formation in C. auris and is required for adhesion to both biotic and abiotic surfaces.

    “The cell wall adhesin Als4 plays a central role in biofilm formation in C. auris and is required for adhesion to both biotic and abiotic surfaces11,14,17,50,52.”

    From The Wor2 phenotypic switching regulator controls biofilm formation in Candida auris (2026) · cites this paper as [14]

    In “Polymer surface attachment by the adhesin SCF1” (page not provided), the paper reports that, among twelve ALS- and IFF/HYR-family deletion mutants tested, only loss of IFF4109 impaired adhesion to the tested polymer surface. Its summary identifies SCF1—not Als4—as critical for biofilm formation and colonization of biological and abiotic surfaces. The copy therefore contradicts the claim that Als4 is required for adhesion to both kinds of surface. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • The murine skin model is widely used to study disease pathogenesis and C. auris-host interactions.

    “In addition, understanding the skin immune responses against C. auris is critical, as the murine skin model is widely used to study disease pathogenesis and C. auris-host interactions [4, 16–20].”

    From Single-cell transcriptomics unveils skin cell specific antifungal immune responses and IL-1Ra- IL-1R immune evasion strategies of emerging fungal pathogen Candida auris (2024) · cites this paper as [17]

    In “SCF1 promotes long-term colonization and virulence” (page unavailable), the paper uses in vivo murine skin to study C. auris colonization and potential interaction with host tissue. It does not establish that the murine skin model is widely used or use that model to study disease pathogenesis; its virulence experiments use intravenous infection instead. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • C. auris possesses a unique cell wall, adhesin proteins, and colonizing factors to thrive in the skin.

    “C. auris possesses a unique cell wall, adhesin proteins, and colonizing factors to thrive in the skin [13, 17, 36]”

    From Single-cell transcriptomics unveils skin cell specific antifungal immune responses and IL-1Ra- IL-1R immune evasion strategies of emerging fungal pathogen Candida auris (2024) · cites this paper as [17]

    The Abstract and Discussion (page not provided) describe C. auris adhesins, including SCF1, that contribute to skin colonization. Our copy does not establish that C. auris has a unique cell wall, so that part of the claim is unsupported. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The C. auris genome codes for several species-specific cell surface glycoproteins that may facilitate C. auris adhesion to different substrates.

    “the C. auris genome codes for several species-specific cell surface glycoproteins that may facilitate C. auris adhesion to different substrates (20, 22).”

    From The <i>Candida auris</i> Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence (2024) · cites this paper as [22]

    The 'Polymer surface attachment by the adhesin SCF1' section reports multiple adhesin genes, and the Discussion links SCF1 and IFF4109 to association with biological and abiotic surfaces. But the paper identifies SCF1 as the distinctive adhesin and describes IFF4109 as conserved; it does not establish that several of the implicated cell-surface proteins are species-specific glycoproteins. Page numbers are unavailable in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Figure 2D cites the wrong source panel for the 23 isolates

    Minor

    The Figure 2 legend says the 23 isolates plotted in panel D are from panel A, but panel A depicts genomic synteny. The legend identifies the 23-isolate adhesion measurements as panel B.

  • SCF1 is described as C. auris-specific despite a homolog in C. haemulonii

    Minor

    The abstract says SCF1 is apparently specific to C. auris, but the results identify a functional SCF1 homolog in C. haemulonii. The paper separately says that reliance on SCF1 for adhesion, rather than the adhesin itself, is specific to C. auris.

  • SCF1 is called required for biofilm formation despite redundant function

    Minor

    The abstract says SCF1 is required for biofilm formation, whereas the results say deletion of both SCF1 and IFF4109 was required to ablate biofilm formation in AR0382. Thus, SCF1 deletion alone did not abolish that phenotype.

3 of 3

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

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.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2023-09-29
Volume
381
Issue
6665
Pages
1461-1467
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.adf8972
PMC
PMC11235122
OpenAlex
W4387128705
Semantic Scholar
e0262fbfb5177b14e3b79fa23998bb062df14f12
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 › Epidemiology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-23.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-23.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review