Candida albicans Mrv8, is involved in epithelial damage and biofilm formation.


Journal

FEMS yeast research
ISSN: 1567-1364
Titre abrégé: FEMS Yeast Res
Pays: England
ID NLM: 101085384

Informations de publication

Date de publication:
01 08 2020
Historique:
received: 15 01 2020
accepted: 24 06 2020
pubmed: 26 6 2020
medline: 25 9 2021
entrez: 26 6 2020
Statut: ppublish

Résumé

Candida albicans is the most common human fungal pathogen that can cause superficial and deep-seated infections in susceptible individuals. Despite its medical importance, the vast majority of C. albicans genes remain of unknown function. Here, we report a role for the lineage-specific gene, MRV8, in host pathogen interactions, mycelial microcolony maturation and biofilm formation. In silico analysis indicated that MRV8 encodes a four-pass transmembrane protein unique to the closely related pathogens C. albicans and Candida dubliniensis. Deletion of MRV8 did not affect C. albicans adherence to, or initial invasion into human oral epithelia, but inhibited mycelial development and strongly reduced epithelial damage. mrv8Δ/Δ cells exhibited a media-dependent defect in biofilm formation and mutant biofilm metabolic activity was enhanced by cyclosporin A. mrv8Δ/Δ biofilms were more tolerant to treatment with caspofungin, but not to fluconazole or amphotericin B. Co-stimulation with calcium chloride and calcofluor white rescued biofilm growth in the presence of caspofungin, and this rescue-effect was Mrv8-dependent. Together, our data demonstrate an important role for a lineage-specific gene (MRV8) in C. albicans biofilm formation, drug tolerance and host-pathogen interactions.

Identifiants

pubmed: 32584995
pii: 5862582
doi: 10.1093/femsyr/foaa033
pmc: PMC7343537
pii:
doi:

Substances chimiques

Antifungal Agents 0
Fungal Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Wellcome Trust
ID : 214317/Z/18/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 09 7377/Z/11/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N006364/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N006364/2
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

© FEMS 2020.

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Auteurs

Anna Carolina Borges Pereira Costa (ACBP)

Department of Biosciences and Oral Diagnosis, São Paulo State University (Unesp), Institute of Science and Technology (ICT); São José dos Campos, Brazil.
Department of Microbial Pathogenicity Mechanisms, Hans-Knoell-Institute, Jena, Germany.
Aberdeen Fungal Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Institute of Medical Sciences, Aberdeen, United Kingdom.

Graziella Nuernberg Back-Brito (GN)

Department of Biosciences and Oral Diagnosis, São Paulo State University (Unesp), Institute of Science and Technology (ICT); São José dos Campos, Brazil.

François L Mayer (FL)

Department of Microbial Pathogenicity Mechanisms, Hans-Knoell-Institute, Jena, Germany.

Bernhard Hube (B)

Department of Microbial Pathogenicity Mechanisms, Hans-Knoell-Institute, Jena, Germany.
Friedrich Schiller University, Jena, Germany.

Duncan Wilson (D)

Department of Microbial Pathogenicity Mechanisms, Hans-Knoell-Institute, Jena, Germany.
Aberdeen Fungal Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Institute of Medical Sciences, Aberdeen, United Kingdom.
Medical Research Council Centre for Medical Mycology, School of Biosciences, University of Exeter, Stocker Rd, Exeter EX4 4QD, Exeter, United Kingdom.

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