Metabolic reprogramming duringCandida albicansplanktonic-biofilm transition is modulated by theZCF15andZCF26paralogs

Abstract

Candida albicansis a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host immune system. To identify novel genes modulatingC. albicansbiofilm formation, we performed a large-scale screen with 2454C. albicansdoxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of theZCF15andZCF26paralogs that encode transcription factors and have orthologs only in biofilm-forming species of theCandidaclade, caused impaired biofilm formation bothin vitroandin vivo. Interestingly, overexpression ofZCF15specifically impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression ofZCF15andZCF26demonstrated their direct role in reprogramming cellular metabolism by regulating glycolytic cycle and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, includingZCF15andZCF26,that appear to control biofilm development through their specific role in metabolic remodeling.