Abstract:
Candida albicans is the most common diploid fungal pathogen in humans and one of the leading causative agents of death in immunocompromised individuals. The fungus harbors an arsenal of factors that are implicated in its virulence. These virulence factors include but are not limited to filamentation inducing transcription factors, adhesins, lipases, proteases, heat shock proteins and superoxide dismutases. The cell wall in a pathogen is crucial in harboring key proteins which constitute many of the abovementioned virulence factors. Dse1 is a 724 amino acid uncharacterized cell wall protein which is involved in cell wall metabolism. The purpose of this study is to characterize the role of Dse1 by generating a dse1 homozygote null strain and comparing the phenotype of the mutant to the wild type parental strain. Characterization included extent of filamentation on solid and liquid media and adhesion to human epithelial cells and biofilm formation. Furthermore virulence was addressed in a mouse model of infection and resistance to oxidative stress and susceptibility to cell surface disrupting agents were also determined. The results of our study show that DSE1 appears to be an essential gene as we were able to generate a heterozygous but not a homozygous null strain. The heterozygous mutant showed a significant degree of haploinsufficiency as it was overfilamentous on both liquid and solid PDA media compared to the parental strain at both 300C and 370C. It also exhibited increased susceptibility to calcuflor white and SDS, both cell surface disrupting agents. However, no differences in response to two other cell surface disruptants Congo red or caspofungin was observed. In addition, the mutant strain showed a decrease in oxidative stress tolerance, exhibited a 30% reduction in biofilm formation and a delay in adhesion compared to the parental strain. These phenotypes were mirrored by a reduction in virulence in a mouse model of infection. Bearing in mind that disruption of cell surface components usually weakens the cell wall resulting in a reduction in filamentation, the hyperfilamentous phenotype of the mutant warrants further investigation.
