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. Our results indicate that loss-of-heterozygosity (LOH) events are frequent and responsible for microevolutions of diploid C. albicans within clades and yet might be counter-selected in the environment. LOH events in commensal isolates have been shown to result mostly from chromosome losses or large mitotic recombination events. We are currently evaluating whether large LOH events are detrimental to C. albicans fitness.

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. It has also identified genes necessary for biofilm cohesiveness and whose products could contribute to the production of the biofilm extracellular matrix. Finally, we have shown that several of these genes play a role in cell wall architecture. The mechanisms underlying antifungal resistance of biofilms are currently investigated.

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 formation and maintenance. Phosphoproteomic and chemogenetic approaches have been used to identify targets of Yak1 and these are currently validated. The chemogenetic approach is now used to study other C. albicans kinases that are involved in morphogenesis.