A Candida auris-specific adhesin, SCF1, governs surface association, colonization, and virulence

Abstract

Candida auris is an emerging fungal pathogen responsible for healthcare-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 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.

One-Sentence Summary:

Surface attachment, colonization, and disease caused by an emerging human pathogen is mediated by a lineage-specific adhesion factor.

Since initial reports of its discovery in 2009, the emerging fungal pathogen Candida auris has become an increasingly common source of life-threatening infection worldwide (1, 2). C. auris is frequently reported in association with nosocomial outbreaks, a characteristic rarely described with other Candida species, and is of urgent concern for public health authorities (3-7). 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 (8-14). C. auris also colonizes indwelling medical devices, which act as a risk factor for the development of invasive disease (15-21). Lapses in diagnostic screening and infection prevention measures are thought to contribute to the increasing rate of C. auris outbreaks (20). The ability of C. auris to robustly colonize a range of living and abiotic substrates is central to its emergence as a global health threat.

Colonization requires the initial physical association and attachment between fungal cells and substrate. For fungal pathogens, attachment is largely mediated by cell surface-exposed adhesin proteins (22). 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). 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. Moreover, their phenotypic importance in C. auris is not well understood (24-26).

To interrogate the role of individual C. auris adhesins in colonization phenotypes, we measured the adhesion between fungal cells and polymer substrates as a model for surface association. We found that C. auris does not primarily rely on conserved adhesins for surface attachment. Instead, we identified Surface Colonization Factor (SCF1), an adhesin specific to C. auris. SCF1 is necessary and sufficient for robust attachment of C. auris cells to polymer substrates. 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. The nonspecific surface association driven by SCF1 does not occur through canonical hydrophobic interactions, but rather through cation-substrate interactions. To explore the clinical relevance of these findings, we investigated the importance of SCF1 in long-term colonization models. 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. These findings offer insight into the genetic and molecular mechanisms by which C. auris mediates surface association, a trait critical to the increasing disease burden of this emerging pathogen.

Results

Polymer surface attachment by the adhesin SCF1

C. auris encodes twelve genes homologous to members of the characterized ALS and IFF/HYR adhesin families (24, 25, 27). We generated individual deletion mutants in the clade I AR0382 background for each adhesin gene to model their impact on surface association. We employed a flow cytometric adhesion assay that measures the ability of cells to attach to dispersed polystyrene microspheres in suspension (Fig. S1) (28). Of the twelve adhesin mutants, only deletion of IFF4109 (B9J08_004109) conferred an adhesive defect, while still failing to completely ablate attachment (Fig. 1A). To investigate the possibility that there were occult adhesive factors, we screened a library of 2,560 insertional mutants, prioritizing mutants exhibiting the most significant defects (Fig. 1B). The greatest loss of adhesive capacity was observed in tnSWI1 (B9J08_003460) and tnBCY1 (B9J08_002818) mutants (Fig. 1B, Fig. 1C, Fig. S2). Compared to the AR0382 parent, the tnSWI1 mutant exhibited no significant transcriptional dysregulation of the ALS or IFF/HYR adhesins, suggesting alternative mediators of adhesion (Fig. 1D). 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). This gene, however, exhibited a putative three-domain architecture consistent with canonical GPI-anchored fungal adhesins (Fig. 1E) (23). Notably, this same gene was also strongly downregulated in the tnBCY1 mutant while IFF4109 was not (Fig. S2). Deletion of the B9J08_001458 ORF in AR0382 conferred a substantial adhesive defect, thus we refer to the gene as Surface Colonization Factor (SCF1) (Fig. 1F). 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). 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).

Fig. 1. Surface Colonization Factor (SCF1) mediates C. auris adhesion to polymer surfaces.

(A) Adhesion of wild type AR0382 or mutants lacking one of twelve genes from ALS or IFF/HYR adhesin families. (B) 2,560 insertional mutants in the AR0382 strain background were screened for adhesion defects by measuring the proportion of cells able to remain attached to a cyclic olefin polymer surface after 3 washes with PBS. Strains are ordered by Z-score rank. Mutants with a Z-score more negative than −3 were considered to have a significant adhesive defect. (C) Adhesion of AR0382 and an insertional SWI1 mutant. (D) RNA-seq comparing the transcriptome of tnSWI1 to AR0382. SCF1 (B9J08_001458) is the strongest dysregulated gene. (E) Predicted domain architecture of Scf1, based on the clade I primary sequence, is consistent with canonical fungal adhesins. (F) Adhesion of adhesin mutants and complements compared to AR0382 (G) Immunofluorescence microscopy using an α-FLAG antibody. Representative images shown for WT AR0382 and AR0382 Δscf1 + SCF1-FLAG. Scale bar = 5 μm. Statistical differences were assessed using one-way ANOVA with Dunnett’s post-hoc test (A), student’s t-test (C), or one-way ANOVA with Tukey’s post-hoc test (G); *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ns: p > 0.05.

The specific reliance on SCF1 and IFF4109 for adhesion despite potential redundancy with other adhesins is reminiscent of other fungal pathogens. For instance, loss of ALS1 alone reduces Candida albicans adhesion, despite the presence of seven other ALS genes (Fig. S3A) (29). In C. auris, adhesins exhibit structural and transcriptional variation, which may explain their functional specificity (Fig. S3B) (25, 26). 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). 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). These findings suggest functional specificity for surface association for SCF1 and IFF4109.

C. auris relies on SCF1 for adhesive plasticity

While many Candida and Saccharomyces adhesins belong to conserved gene families, we identified homologs of SCF1 only in C. auris and the closely related Candida haemulonii species and not in other members of the haemulonii complex (Fig. 2A). 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). 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).

Fig. 2. C. auris uniquely relies on SCF1 for adhesive plasticity.

(A) Synteny schema depicting SCF1 and the conservation and orientation of adjacent ORFs. Genomic loci are shown in comparison to C. auris. Putative SCF1 homologs were only identified in C. auris and C. haemulonii. (B) Adhesion of 23 C. auris clinical isolates from all 5 clades. (C) Adhesion of 19 C. albicans clinical isolates from five clades. FC = Fingerprint Clade. (D) SCF1 transcript abundance (top panel) but not IFF4109 transcript abundance (bottom panel) is associated with adhesion to polystyrene in the same 23 C. auris isolates from (A). Log₂FC are expressed relative to AR0382. Each point signifies the mean of three biological replicates. Pearson correlation coefficient and p-value indicated. Isolates that do not encode IFF4109 are not indicated in the bottom panel. (E) Comparison of adhesion between two Clade I isolates: AR0382 and AR0387. Overexpression of SCF1 using the strong TEF1 promoter (right panel) is sufficient to drive adhesion in the poorly adhesive AR0387 background (left panel). Statistical differences were assessed using one-way ANOVA (A) and (B), with Tukey’s post-hoc test (D) or student’s t-test (D); *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ns: p > 0.05.

To investigate the generalizability of the reliance on SCF1 and the variability between C. auris strains, we measured adhesion for 23 C. auris isolates representing all five clades and diverse geographic origins of C. auris. These strains exhibited substantial adhesive variation, regardless of clade (p=2x10⁻¹⁶, F=35.06, one-way ANOVA) (Fig. 2B). 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). Interestingly, substantial variation in adhesion was observed even between genetically similar isolates of C. auris, e.g., AR0382 and AR0387, which differ by only 206 coding SNPs (Fig. 2B). In the poorly adhesive AR0387, SCF1 was the most down-regulated gene compared to the highly adhesive AR0382, reminiscent of the poorly adhesive tnSWI1 mutant (Fig. S5A, Fig. 1D). The transcriptome of AR0387 showed little overlap with that of the tnSWI1 strain, however, indicating dysregulation of SCF1 in AR0387 is not caused by a SWI/SNF complex defect (Fig. S5B). Furthermore, we observed no nucleotide variants in the SCF1 ORF or neighboring intragenic regions between AR0382 and AR0387.

Transcript abundance of SCF1 was tightly positively correlated with adhesion across isolates, regardless of clade (r=0.87, p=8.4 x 10⁻⁸) (Fig. 2D). In contrast, we observed no association between transcriptional control of IFF4109 and adhesion (r=0.3, p=0.25) (Fig. 2D). Experimentally, transcriptional overexpression of SCF1 was sufficient to elevate adhesion in the otherwise poorly adhesive isolate AR0387 (Fig. 2E). Importantly, the magnitude of overexpression using the TEF1 promoter (approximately 2⁸-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 2⁹-fold change) (Fig. 2D, Fig. 2E). These data show that adhesive variation between C. auris isolates is associated with SCF1 expression variation.

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). We tested whether allelic variation also contributed to the adhesive variation among isolates. Overexpression of the native SCF1 allele in AR0381, a poorly adhesive clade II isolate, was sufficient to increase attachment (Fig. S6A). However, overexpression of the clade I SCF1 allele from AR0382 further elevated adhesion, despite similar levels of overexpression (Fig. S6A). Interestingly, in the clade I AR0382 background, which relies strongly on SCF1 for adhesion, complementation of the Δscf1 mutant with either the clade I or the clade II SCF1 allele resulted in similar levels of rescue of the adhesive phenotype (Fig. S6B). 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.

SCF1 and IFF4109 have distinct nonspecific mechanisms

The reliance on SCF1 for surface association is complicated by the genetic interaction with IFF4109, where deletion of both does not result in a more severe adhesive defect than deletion of SCF1 alone (Fig. 1F). Loss of one adhesin did not result in dysregulation of the other, suggesting the interaction is not a regulatory one (Fig. S7). One possibility is that the two genes contribute to adhesion through distinct but complementary physical mechanisms. For other Candida species, adhesion to abiotic substrates is often nonspecific, with adhesins promoting affinity for hydrophobic substrates (32-34). The highly adhesive AR0382 strain exhibited elevated cell surface hydrophobicity compared to the poorly adhesive AR0387 (Fig. 3A, Fig. 3B). Deletion of the IFF4109 adhesin in AR0382 reduced cell surface hydrophobicity, which was rescued to wild type levels by complementation (Fig. 3A, Fig. 3B). In contrast, deletion or overexpression of SCF1 did not significantly impact cell surface hydrophobicity in either AR0382 or AR0387 (Fig. 3A, Fig. 3B).

Fig. 3. IFF4109, but not SCF1, mediates adhesion through cell surface hydrophobicity.

(A) Representative images from Microbial Attachment to Hydrocarbons (MATH) assay. Hydrophobic cells are sequestered from the aqueous phase (Aq) to the aqueous-hydrocarbon interface (Int) after mixing with the hydrocarbon phase (HC). (B) Proportion of cells sequestered out of the aqueous phase during MATH assay. (C), (D) Cells were allowed to attach to a hydrophobic, untreated polystyrene surface (C) or a hydrophilic, vacuum plasma treated polystyrene surface (D) for 1 hour. The surface was washed and the proportion of cells that remained attached after washing was measured. Statistical differences were assessed using one-way ANOVA with Tukey’s post-hoc test (B), (C), and (D) or student’s t-test (C) and (D); *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ns: p > 0.05.

Elevated cell surface hydrophobicity likewise promotes affinity for hydrophobic substrates (33). We measured the adhesion of C. auris isolates to both an untreated hydrophobic polystyrene surface and a polystyrene surface modified using a vacuum plasma treatment to become strongly hydrophilic. Both IFF4109 and SCF1 mediated adhesion to the hydrophobic substrate (Fig. 3C). However, only SCF1 mediated adhesion to the hydrophilic substrate, showing that SCF1 is not dependent on hydrophobicity (Fig. 3D). 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).

To investigate the mechanism of Scf1 adhesion, 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). 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). Furthermore, model confidence dwindles outside the Fibronectin fold, suggesting substantial variation from Flo11 adhesins (Fig. S9). In its primary sequence, the SCF1 N-terminal domain exhibits an enrichment of arginine and lysine residues compared to other yeast adhesins (Table S2). 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). We reasoned that if Scf1 relied on such interactions, adhesion could be inhibited by a saturating concentration of cations at the substrate interface that could not be competitively displaced by SCF1. Consistent with this hypothesis, high concentrations of arginine in solution were sufficient to ablate AR0382 adhesion (Fig. 4A). 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).

Fig. 4. Specific cationic residues are critical for Scf1-mediated surface association.

(A), (B) WT AR0382 adhesion in the presence of increasing concentrations of arginine (A) or 1 M additives (B). (C) Predictive model of the Scf1 N-terminal domain with two neighboring cationic-aromatic clusters highlighted. (D) Adhesion of wild type AR0382, a mutant lacking SCF1, or AR0382 Δscf1 + SCF1-FLAG mutants encoding the wild type SCF1 allele or alleles containing the indicated mutations. (E) TMR-labelled 13-amino acid peptides corresponding to the wild type Scf1 sequence (residues 50-62) or the same sequence with the indicated mutations incubated with the same polystyrene microspheres used to measure adhesion in (D). Scale Bar = 5 μm. (F) Quantification (MFI) of peptide binding to individual polystyrene microspheres as in (E) measured by TMR epifluorescence, corrected for background fluorescence. Each point represents an individual microsphere. Colored points represent averages of individual experiments, used for statistical analysis. Statistical differences were assessed using one-way ANOVA with Dunnett’s post-hoc test (A), (B) or one-way ANOVA with Tukey’s post-hoc test (D) and (F); *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ns: p > 0.05.

We next investigated whether specific cationic regions or residues were critical for Scf1 activity. We generated point mutations in cationic residues in different areas of the N-terminal domain, focusing on residues that clustered with aromatic groups, as this pattern potentiates electrostatic adhesion (Fig. S10A) (42). 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). Mutating the entire cation-aromatic cluster, H52 H53 R54 R55, resulted in a similar adhesive defect (Fig. 4C, Fig. 4D, Fig. S11). Notably, a nearby cation-aromatic cluster, K44-K49, which was modeled to be less surface-exposed, was not required for adhesion (Fig. 4C, Fig. 4D, Fig. S11). To determine whether surface exposure of the HHRR cluster (res. 52-55) would be sufficient to promote adhesion, we synthesized peptides corresponding to Scf1 residues 50-62 with the intact wild-type cluster or the HHRR residues mutated. The wild-type peptide adhered to polystyrene microspheres, but mutation of the HHRR cluster completely ablated this ability (Fig. 4E, Fig. 4F). Interestingly, similar patterns of cation-aromatic clusters are also abundant in some lipid-binding proteins (40, 43). 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).

SCF1 promotes long-term colonization and virulence

We next investigated the impact of SCF1 and IFF4109 on other aspects of surface colonization. We measured the importance of these adhesins for biofilm growth, which can promote prolonged environmental persistence (11, 44-46). 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). Expression of SCF1 alone in otherwise biofilm-incompetent isolates was sufficient to establish biofilm colonization (Fig. S13B, Fig. S13C, Fig. S13D, Fig. S13E). This pattern continued for in vivo biofilms, where loss of SCF1 and IFF4109 ablated the ability of AR0382 to colonize the luminal surface of a polyethylene rat central venous catheter, and overexpression of SCF1 was sufficient to potentiate AR0387 colonization (Fig. 5A, Fig. 5B).

Fig. 5. SCF1 mediates host colonization and infection phenotypes.

(A), (B) Polyethylene central venous catheters were set in rat jugular veins and inoculated intraluminally with C. auris. Representative scanning electron microscopy images of the luminal catheter surface are shown from catheters collected 24 hrs after infection. Scale bars: 400 μm (100x), 40 μm (1000x), 5 μm (5000x). (C), (D) Full thickness human skin explants were colonized with C. auris for 24 hrs before washing to remove unassociated cells. Representative scanning electron microscopy images of the skin surface following washing are shown. Scale bars: 20 μm (1000x), 4 μm (5000x). (E), (F), (G) Immunosuppressed mice were infected intravenously (via tail vein injection) with 5 x 10⁷ C. auris cells. Histopathology sections of the kidneys 7 days post infection (E), (F) were stained with PAS. Magenta color indicates lesion areas. Ten infected mice for each strain were monitored for survival for 21 days (G). Statistical comparisons of overall survival were assessed using the Mantel-Haenszel log-rank test with Benjamini-Hochberg correction. *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ns p > 0.05.

We then investigated whether biological surface association followed the same reliance on these adhesins. Again, we observed that loss of SCF1 and IFF4109 diminished the ability of AR0382 to colonize ex vivo human skin explants and in vivo murine skin, while overexpression of SCF1 potentiated skin colonization by AR0387 (Fig. 5C, Fig. 5D, Fig. S14). Given this potential for interaction with host tissues, we also investigated the importance of these adhesins in disseminated infection. Histopathological examination of tissues collected from mice 7 days after intravenous C. auris infection revealed that loss of SCF1 and IFF4109 reduced AR0382 dissemination to the kidneys and heart, while overexpression of SCF1 in AR0387 was sufficient to increase fungal lesions (Fig. 5E, Fig. 5F, Fig. S15). 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). 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).

Discussion

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). Our findings suggest 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. Interestingly, the other conserved adhesin genes appeared to not mediate surface association. Whether this is the product of functional or regulatory divergence remains to be explored. 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. The widespread plasticity around a single genetic element responsible for diverse clinically-relevant phenotypes could be problematic in outbreak settings. While SCF1 and IFF4109 contribute to host infection and colonization, the mechanisms of their interaction with host systems remain unclear. Understanding how variable adhesion allows C. auris to mediate infection is likely to offer therapeutic insights. Prior work suggests vaccination or monoclonal antibody therapy targeting Als or Iff/Hyr adhesins may offer protection against lethal C. auris infection (27, 47). Furthermore, the complementary function of SCF1 and IFF4109 with divergent mechanisms suggests C. auris has evolved the capacity for promiscuous surface association and colonization. Mediation of hydrophobic interactions is largely conserved among fungal adhesins, consistent with the adhesive mechanism of the conserved IFF4109 (32-34). The cation rich SCF1, however, appears to functionally resemble proteins from bivalve, barnacle, and Vibrio adhesion systems. For these organisms, cation-dependent surface interactions promote adhesion in aqueous and highly ionic environments (36-39). 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). Development of unique adhesion biology may in part explain the tenacity of this organism on medically-relevant substrates. Still, differential utilization of SCF1 by different isolates suggests an unknown selective pressure may govern its expression. Understanding this adaptation and its clinical consequences more fully may offer important insights into the outbreak potential of this pathogen.

Overall, our work characterizes of the adhesin machinery used by C. auris for surface association and colonization. The identification of SCF1 and the characterization of the genetic determinants of adhesion add to the growing understanding of the pathobiology this emerging organism.