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

Anna Carolina Borges Pereira Costa,François L Mayer,Bernhard Hube,Duncan Wilson,Graziella Nuernberg Back-Brito

doi:10.1093/femsyr/foaa033

Abstract

ABSTRACT 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.

Highlights

Candida albicans is normally a commensal member of the human microbiota and can cause disease when an imbalance in host immunity or a disturbance of the normal microbiota composition allows the transition to a pathogenic lifestyle (Gow and Hube 2012)
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. mrv8 / cells exhibited a media-dependent defect in biofilm formation and mutant biofilm metabolic activity was enhanced by cyclosporin A. mrv8 / biofilms were more tolerant to treatment with caspofungin, but not to fluconazole or amphotericin B
The mrv8 / formed smaller micro-colonies than the wild type and complemented strains (Fig. 1E). These data indicate that Mrv8 is dispensable for the initial filamentation, adhesion and invasion events associated with C. albicans-epithelial infection, but that the mutant’s attenuated damage capacity is likely due to defective mycelialrelated growth

Summary

Introduction

Candida albicans is normally a commensal member of the human microbiota (mycobiota) and can cause disease when an imbalance in host immunity or a disturbance of the normal microbiota composition allows the transition to a pathogenic lifestyle (Gow and Hube 2012). The pathogenicity of this fungus is mediated by a number of factors including adhesion to host cells, invasion and damage, which is predominantly caused by secretion of the cytolytic toxin, candidalysin (Moyes et al 2016).

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