GPI Anchor Biosynthesis Regulates Ergosterol Biosynthesis and Hyphal Morphogenesis

Candida albicans is an opportunistic fungal pathogen that switches from yeast form to pathogenic fungal form.GPI anchoring is a post translational modification which takes place in endoplasmic reticulum by multiple step pathway.Here first step is the formation of GPI-N-acetyl glucosaminyl phosphatidylinositol (GlcNAcPI) from uridinediphosphate- N-acetylglucosamine(UDP-GlcNAc) and phosphatidylinositol (PI). It consists of six different subunits Gpi1,Gpi2, Gpi3,Gpi15, Gpi19, and Eri1. Our laboratory has studied two different subunits, Gpi2 and Gpi19, and it is reported that subunit Gpi19 mutually coregulates with ergosterol biosynthesis. Gpi2regulates hyphal morhphogenesis via Ras signaling and governs pathogenecity. Both Gpi2 and Gpi19 subunits negatively regulate each other. In addition, subunit Gpi15 is also studied in our lab. By observing phenotypic effects it was found that the single allele disruption of GPI15(GPI15 heterozygote) makes the strain azole sensitive and hypofilamentous compared to wild type. Deletion of one allele of GPI19 and GPI2 in the GPI15 heterozygote makes it further sensitive to azoles and hypofilamentous while overexpression reverts the phenotypic effects. We conclude that Gpi15 governs both ergosterol biosynthesis and Ras signaling via Gpi19 and Gpi2 and that Gpi15 can act as a good antifungal target .