Fungal infections represent a significant, and yet poorly controlled, part of nosocomial infections. The Fungal Biology and Pathogenicity Unit is studying three aspects of the biology of Candida albicans, a diploid and polymorphic yeast responsible for the vast majority of opportunistic fungal infections in humans.

Genetic diversity of Candida albicans

We have established C. albicans Multi Locus Sequence Typing (MLST) and applied it to clinical and commensal C. albicans strains. In collaboration with Aberdeen University, we have shown that almost all of 1400 C. albicans isolates can be assigned by MLST to one of 17 clades. Current research is aimed at investigating at a genomic level the extent of the genetic diversity that distinguishes isolates within or between clades. Our results indicate that microevolutions of diploid C. albicans within clades are frequently mediated by loss-of-heterozygosity (LOH) events (chromosome losses or large mitotic recombination events). Yet, these large LOH events appear counter-selected in the environment.

Biofilm formation by Candida albicans

Biofilms are microbial communities that develop in association with a biotic or abiotic surface. They form a protected environment where micro-organisms adopt a specific physiology. Candida biofilm cells have an elevated resistance to antifungals and this often results in sequels following an apparently successful antifungal treatment. Functional analysis of C. albicans genes over-expressed upon biofilm formation has confirmed that the yeast-to-hypha transition is critical for biofilm formation and has identified genes necessary for biofilm cohesiveness. We have shown that several of these genes play a role in cell wall architecture. Our recent results suggest that antifungal resistance of biofilms might be mainly mediated by entrapment of the antifungals in extracellular matrix materials.

Protein kinases and regulation of morphogenesis

Morphogenesis is central to the virulence of C. albicans. We have shown that the C. albicans Yak1 kinase regulates hyphal emergence and maintenance. Different approaches – transcriptomics, phosphoproteomics, chemogenetics, overexpression screens – are now combined to unravel the role of Yak1 and other signaling components in filamentation.

Keywords: Candida albicans, biofilm, antifungal resistance, epidemiology, candidemia, candidosis, cell wall proteins, kinase, signaling

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