The yeast pathogen Candidozyma (Candida) auris can form biofilms, which contribute to its virulence and nosocomial transmission. In this study, we identified the transcription factor Wor2 as a negative regulator of biofilm formation in C. auris. Wor2 hyperactivation in a strain of clade IV via the use of a protein tagging strategy resulted in downregulation of two important adhesins, SCF1 and ALS4112, and decreased biofilm-forming capacity. We showed that the impact on biofilm was predominantly mediated via decreased SCF1 expression in this strain. However, results of adhesion assays on inert surfaces and human keratinocytes found relatively modest roles of Wor2 and Scf1 in this process, suggesting that their effect on biofilm formation is complex and not limited to the adhesion step. Finally, analyses of other strains from different clades identified three distinct WOR2 genotypes, with variable WOR2 expression levels and distinct impacts of WOR2 deletion on biofilm formation. Notably, Wor2 negatively regulated biofilm in strains of clades I, III, and IV with distinct profiles of SCF1/ALS4112 expression, while it had no impact on biofilm in a clade II strain. Taken together, this study showed that Wor2 exhibited some distinct genotypic evolution in C. auris resulting in clade- or strain-specific regulatory roles and pathways in biofilm formation.IMPORTANCECandidozyma (Candida) auris is a pathogenic yeast exhibiting a particular capacity for interhuman transmission via medical instruments, which was the cause of nosocomial outbreaks of candidemia. Adhesion to inert surfaces and subsequent biofilm formation is therefore important for C. auris propagation. This work highlights the role of the transcription factor Wor2 as a negative regulator of biofilm formation in C. auris. In a strain of clade IV, Wor2 was shown to downregulate two important adhesins (SCF1 and ALS4112). Interestingly, Wor2 exhibited different genotypes across C. auris clades and strains, which were associated with distinct differential expression of WOR2, ALS4112, and SCF1, and possibly distinct roles in biofilm formation.
Louvet et al. (Mon,) studied this question.