The Candida auris Adhesin Scf1 Mediates Broad Host-Protein Recognition through Shared Adhesive Regions
Year: 2026
Type: preprint
Abstract: Candida auris ( C. auris ) is a rapidly emerging, multidrug-resistant fungal pathogen whose persistence is partly driven by adhesion to host tissues and abiotic surfaces. Surface-colonization factor 1 (Scf1) is a C. auris -specific adhesin implicated in surface adhesion, biofilm formation, virulence, and persistence in health care settings. However, the human proteins recognized by Scf1 and the response of these interactions to hydrodynamic flow and shear stress were previously unknown. Using yeast surface display, spinning-disk adhesion and FACS-based binding assays, we show that the N-terminal adhesive domain of Scf1 binds the cell-surface glycoprotein mucin-1 (MUC1) and the extracellular matrix proteins vitronectin (VIT) and fibronectin (FN), while exhibiting no detectable binding to collagen I, collagen IV, or fibrinogen. Hydrodynamic shear stress was found to tune ligand preference, with VIT being preferred at equilibrium and MUC1 being the more strongly bound target under flow. Epitope mapping by deep mutational scanning (DMS) of Scf1 against MUC1, VIT and FN identified shared binding patches consisting of predominantly cationic and aromatic residues involved in recognizing all three ligands. Mutations within these regions reduced binding without compromising yeast display expression levels, indicating that these residues are involved in ligand recognition and that mutations at these positions do not compromise global protein folding stability. These findings establish the Scf1 N-terminal domain as a semi-promiscuous ligand-recognition domain for a structurally diverse set of human proteins and suggest that a mechanosensitive adhesion mechanism contributes to C. auris colonization.
Institutions: University of Basel, ETH Zurich
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G697443731
OpenAlex ID: W7212025448