Characterization of Hwp2, a Candida albicans putative GPI-anchored cell wall protein necessary for invasive growth

Abstract

Various factors are thought to be responsible for Candida albicans virulence, such as lipases, proteases and adhesins. Many of these factors are GPI-anchored cell surface proteins responsible for pathogenicity. Hwp2 is a putative GPI-anchored protein. The purpose of this study is to characterize the role of Hwp2 regarding filamentation on various filamentation-inducing and non-inducing solid and liquid media, virulence in a mouse model of disseminated candidiasis, and drug resistance to six widely used antifungal agents, by creating a homozygous null hwp2 strain and comparing it with the parental and a revertant HWP2+strain. It was observed that an hwp2Δ strain was highly filamentation-deficient on solid agar media as opposed to most liquid media tested. 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. These results indicate a possible role for Hwp2 in adhesion and invasiveness. Finally a previously unidentified 37-amino-acid-long, stretch of Hwp2, possibly involved in protein aggregation, was found to align with high sequence identity and exclusively to C. albicans cell wall proteins.