Candida glabrata is the second most common pathogenic Candida species of humans. It is normally found among the resident microbiota of healthy individuals’ mucosae, but can cause disease when host barriers or immunity are impaired. Disease states range from superficial skin and mucosal infections to systemic infections. The transition from commensalism to pathogenicity is well described in C. albicans and it occurs in three major steps: adhesion, invasion and damage of the host cells. The same cannot be said about C. glabrata, where the same transition is still poorly elucidated. Since C. glabrata is phylogenetically very different from C. albicans and lacks some of the major C. albicans virulence attributes, such as its ability to form hyphae, it is unlikely that the steps leading to epithelial damage have common mechanisms between these two very different fungi. 

In this study, we aim to investigate the adhesion, invasion and damage potential of C. glabrata during infection of vaginal human epithelial cells (ECs) in vitro and gain more insight into its pathogenicity mechanisms.

C. glabrata adhered to ECs similar to C. albicans, but no invasion was observed. Although C. glabrata did not cause epithelial damage 24 h post infection (p.i.), significant epithelial damage was recorded 48 h p.i. To identify genes required for epithelial damage, a large-scale C. glabrata deletion library (619 strains) was screened. Sixteen mutants lacking genes associated with cell wall organization and cell adhesion showed reduced damage potential. 

These data suggest a hyphal independent damage mechanism of C. glabrata, which requires adhesion, but not invasion. In further studies, we aim at characterizing the role of damage associated genes and elucidating the processes leading to damage.


5 / Candida glabrata epithelial cell damage