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

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.

Functional Redundancy inCandida aurisCell Surface Adhesins Crucial for Cell-Cell Interaction and Aggregation

“…We initially identified gene B9J08_001458 as an ortholog of the C. albicans RBT1 gene in agreement with a previous report 31 ; however, this gene has since been renamed SCF1 28 . In exploring the similarity between the C. auris Scf1 and the C. albicans Rbt1 adhesin, comparative analysis of protein domain organization was performed.…”

“…Most notable among the genes that are more highly expressed in the aggregative strain were B9J08_001458 and B9J08_004112, which encode homologs of C. albicans RBT1 and ALS5 , respectively 31,34,35 . Recently, B9J08_001458 was described as unique to C. auris and was named SCF1 by Santana et al 28,36 ; protein domain analysis shows that both Scf1 and Saccharomyces cerevisiae Flo11p share a N-terminal Flo11 domain 28 . The Flo adhesin family initially discovered in brewer’s yeast (S. cerevisiae) has the ability to form cellular aggregates induced by shear force 18,29 .…”

“…Identified polymorphisms enriched in weakly-aggregating strains of C. auris were found to be associated with loss of cell surface proteins; furthermore, amplification of the subtelomeric adhesin gene ALS4 was associated with enhanced adherence and biofilm formation 26,27 . In addition, cell aggregation was shown to increase at higher growth temperatures, suggesting that aggregation is a complex phenomenon that may be linked to the ability to form extracellular matrix and cell surface amyloids 26,28 .…”

Candida aurisundergoes adhesin-dependent and -independent cellular aggregation

“…Indeed, phylogenetic analysis indicates that ALS-family members cluster by species and not by a particular type of ALS from different species [28], this also seems to be the case for Hyr/Iff-like adhesins [30]. To prevent further confusion, we follow the solution proposed by O’Meara and colleagues [31] to use the unique number in the systematic ID as gene number. And therefore, B9J08_004112/XP_028889036 should be called Agglutinin- L ike S equence 4112 ( ALS4112 /Als4112), B9J08_002582 ALS2582 , and B9J08_004498 ALS4498 .…”

“…Whether this particular adhesin is involved in biofilm formation, adherence to host cells, or adherence to other surfaces (medical equipment) remains to be tested. Indeed, a recently identified C. auris -specific adhesin, Scf1, contributes to virulence by promoting adhesion to both biological and abiotic surfaces [31].…”