Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4

Author summaryThe emerging fungal pathogen Candida auris has rapidly spread worldwide in the past several years. This fungus is considered to be a "superbug" pathogen due to its multidrug-resistant properties and high rates of transmission in clinical settings. Unlike other pathogenic species in the Candida genus, many clinical isolates of C. auris can form a unique morphology, namely a multicellular aggregating phenotype, that is thought to be caused by defects in cell division. In this study, we report a new aggregating form observed from two clinical isolates of C. auris with increased adhesion and biofilm forming capacity. Genomic analysis demonstrated that amplification of the subtelomeric adhesin gene ALS4 is the reason behind the strain's enhanced adherence and biofilm forming capacities. Compared to the previously characterized nonaggregative/yeast-form and aggregative-form strains, this new Als4-mediated aggregative-form strain of C. auris displays many unique characteristics in terms of its biofilm formation, surface colonization, and virulence. Candida auris is an emerging multidrug-resistant fungal pathogen and a new global threat to human health. A unique morphological feature of this fungus is its multicellular aggregating phenotype, which has been thought to be associated with defects in cell division. In this study, we report a new aggregating form of two clinical C. auris isolates with increased biofilm forming capacity due to enhanced adherence of adjacent cells and surfaces. Unlike the previously reported aggregating morphology, this new aggregating multicellular form of C. auris can become unicellular after treatment with proteinase K or trypsin. Genomic analysis demonstrated that amplification of the subtelomeric adhesin gene ALS4 is the reason behind the strain's enhanced adherence and biofilm forming capacities. Many clinical isolates of C. auris have variable copy numbers of ALS4, suggesting that this subtelomeric region exhibits instability. Global transcriptional profiling and quantitative real-time PCR assays indicated that genomic amplification of ALS4 results in a dramatic increase in overall levels of transcription. Compared to the previously characterized nonaggregative/yeast-form and aggregative-form strains of C. auris, this new Als4-mediated aggregative-form strain of C. auris displays several unique characteristics in terms of its biofilm formation, surface colonization, and virulence.