Abstract:
The human fungal pathogen Candida albicans is one of the leading causative agents
of death in immunocompromised individuals. Many factors have been implicated in
virulence including filamentation inducing transcription factors, adhesins, lipases, and proteases. Many of these factors are GlycosylPhosphatidylInositol (GPI)- anchored cell surface antigenic determinant proteins. Pga1 is a short 133 amino
acid protein shown to be up regulated during cell wall regeneration. The purpose of this study is to characterize the role of Pga1 as far as filamentation on solid and liquid filamentation and non-filamentation inducing media, susceptibility to cell surface disrupting agents, oxidative stress to a potentially lethal dose of hydrogen peroxide. Furthermore, virulence in a mouse model of disseminated candidiasis, adhesion to human epithelial cells and biofilm formation will be characterized. This
will be performed by creating a homozygous pga1 null strain and comparing the
iv phenotype to the parental strain. It was observed that the null phenotype was over filamentous on both liquid and solid potato dextrose agar (PDA) media compared to the parental strain at both 300C and 370C. In addition the mutant strain showed less oxidative stress tolerance. The mutant exhibited reduced susceptibility to sodium dodecyl sulfate (SDS), but increased susceptibility to calcofluor white, both being cell surface disrupting agents. However, no differences in response to Congo red or caspofungin were observed. Furthermore the mutant exhibited a 50% reduction in adhesion and a 33% reduction in biofilm formation compared to the parental strain, which was reflected as a reduction in virulence. This data is interesting; bearing in mind that disruption of many cell surface components usually weakens the cell wall, resulting in hypersensitivity to the utilized agents and a reduction in filamentation. Whether the cell compensates a pga1 deletion and responds by up regulating other cell surface components is possible.
