Metabolic reprogramming during Candida albicans planktonic-biofilm transition is modulated by the transcription factors Zcf15 and Zcf26
2024
Rai, Laxmi Shanker | Chauvel, Murielle | Sanchez, Hiram | Wijlick, Lasse, Van | Maufrais, Corinne | Cokelaer, Thomas | Sertour, Natacha | Legrand, Mélanie | Sanyal, Kaustuv | Andes, David R. | Bachellier-Bassi, Sophie | D'Enfert, Christophe | Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF) ; Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Gandhi Institute of Technology and Management (GITAM) | University of Wisconsin-Madison | Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB ; Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité) | Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) | Bose Institute [Kolkata, India] | This project was supported by a grant from the Fondation pour la Recherche Médicale (FRM, DBF20160635719) to CdE. Work in the laboratory of CdE is supported by the Agence Nationale de Recherche (ANR-10-LABX-62-IBEID). | ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
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Show more [+] Less [-]German. Candida albicans is 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 modulating C. albicans biofilm formation, we performed a large-scale screen with 2,454 C. albicans doxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of the ZCF15 and ZCF26 paralogs that encode transcription factors and have orthologs only in biofilm-forming species of the Candida clade, caused impaired biofilm formation both in vitro and in vivo. Interestingly, overexpression of ZCF15 impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression of ZCF15 and ZCF26 demonstrated their role in reprogramming cellular metabolism by regulating central metabolism including glyoxylate and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, including ZCF15 and ZCF26, that appear to control biofilm development through their specific role in metabolic remodeling.
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