Genetic and phenotypic characterization of commensal and clinical Candida albicans isolates reveals heterogeneous distribution of adherence and invasiveness properties

EA MERS CT3 EJ3National audienceConsidering Candida albicans as a primarily clonal model of reproduction, distinct lineages of C. albicans could propagate independently, each clonal lineage having possibly variations in biological traits contributing to the pathogenicity of the fungus such as adherence or the yeast-hyphae transition. Indeed, adherence to epithelial cells is considered a virulence trait of C. albicans since contributing to the first contact of the fungus with the host’s epithelial layers. Moreover the ability of C. albicans to switch from the yeast to the hyphae form is an important determinant of C. albicans virulence since favoring invasion of the fungus into the host’s tissues. Using a Multi-Locus Microsatellite Typing, (MLMT) approach, we previously addressed the question of the pathogenicity of lineages of C. albicans with regard to their origin in three series of C. albicans isolates : 82 commensal isolates collected in healthy individuals, 46 invasive bloodstream isolates and 46 of non-bloodstream clinical isolates. In the current study, invasiveness (i.e. cytotoxicity effect) and adherence to epithelial cells of representative strains of the 3 series previously characterized at the genotypic level were investigated in the Caco-2 in vitro model of human intestinal barrier. Correlations between invasiveness, adherence, genotype and origin were then investigated. Principal component factor analysis failed to reveal specific correlation between genotypic and phenotypic characters for all of the strains studied. However, it was possible to group strains into three clusters based on their capabilities to adhere to and to invade intestinal cells. Interestingly, some clinical strains presented a decrease in their cytotoxic effect associated with a defect in their filamentation capability. To illustrate these observations, the clinical strain n°926 was further characterized in vitro with regard to its filamentation capabilities as compared to the reference strain C. albicans SC5314. Colony morphology on specific agar media reported a strong defect in its filamentation ability. This was confirmed by microscopic observations in specific liquid media. Despite similar adherence capability to epithelial cells, cytotoxicity of the strain n°926 was significantly lower than the reference strain C. albicans SC5314. These data suggest that (i) invasion of epithelial cells is mainly driven by the ability of C. albicans to switch from the yeast to the hyphal form and (ii) natural C. albicans strains could harbor atypical defect in their filamentation capabilities. Experiments are in progress in a mouse model of disseminated candidiasis originating from the gastro-intestinal tract to confirm the defect in filamentation capabilities of C. albicans natural strains observed in vitro