Characterization of HWP2 a putative GPI anchored candida albicans cell surface protein. (c2007)

Abstract

The yeast Candida albicans is one of the leading fungal pathogens caus1l1g death in immunocompromised individuals. Various factors are thought to be responsible for vi rulence, such as lipases, proteases and adhesins. Many of these factors are glycosylphosphatidylinositol (GPI) anchored cell surface antigenic determinant proteins responsible for pathogenicity. Hwp2 is a putative GPI anchored protein. The purpose of this study is to characterize the role of Hwp2 as far as filamentation on solid and liquid media, virulence in a mouse model of disseminated candidiasis, drug resistance to six widely used antifungal agents, and white opaque switching, by creating a homozygous null hwp2 strain. It was observed that an hwp2LJ strain was highly filamentation deficient on corn meal and sabouraud solid agar media but not on most liquid media tested, with 100% serum being a minor exception. Furthermore the mutant strain was slightly reduced in virulence compared to the wild strain since all mice infected with the control strain died after 6 days of injection compared with 11 days for the mutant. No discrepancy between the control and mutant was observed as far as drug resistance using the E-test method, or white opaque switching. These results indicate a possible role for Hwp2 in adhesion and invasiveness. Finally aligning the Hwp2 sequence with its two closest homologues, Hwp 1 and Rbtl revealed a small conserved region of high homology found twice in each protein that might reflect a possible sequence necessary for structural integrity.