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.
