Genome dynamics and virulence in the human pathogen Candida glabrata

Abstract: Although the yeast Candida glabrata is considered to be a part of the commensal microflora in healthy individuals, during the last years it has been frequently isolated from patients with mucosal and systemic fungal infections. Now it is considered as the second most frequently isolated pathogenic yeast after Candida albicans. Despite its name, C. glabrata is phylogenetically a closer relative to Saccharomyces cerevisiae than to C. albicans. Apparently, C. glabrata has only recently changed its life style and become a successful opportunistic pathogen. It has been found that this yeast can rearrange its genome to cope the surrounding environments, and I show hereby that clinical isolates of C. glabrata show enormous genomic plasticity. How this yeast reshuffles its genome to become a successful human pathogen remains to be elucidated. During the last decades, several studies have been conducted to find out the mechanisms behind the pathogenicity of C. glabrata. Some studies have shown that C. glabrata can adapt to the harsh conditions by changing the number and size of chromosomes but intra- and inter-chromosomal segmental duplications have also been observed. Moreover, C. glabrata has become of great interest for researchers due to its rapid development of antifungal drug resistance. Therefore, the mechanisms involved in genome rearrangement of C. glabrata to survive as a human pathogen and how it tolerates azole antifungal therapy is an interesting aspect to study. In this study I also developed a new tool, RNAi, to study putative virulence genes.