GPI Anchor Biosynthesis A study of the role of PIG H GPI15 in Candida albicans: Studying GPI anchor biosynthesis in Candida albicans

Abstract

GPI anchoring is a post translational modification that takes place in the endoplasmic reticulum by multiple step pathway and results in the formation of GPI anchored proteins. In Candida albicans GPI anchored proteins are responsible for causing virulence during infection. newline The focus of this work is the first step of GPI biosynthesis. The first step is the formation of GPI N acetyl glucosaminyl phosphatidylinositol GlcNAcPI from Uridinediphosphate N acetylglucosamine UDP GlcNAc and phosphatidylinositol PI. In Candida albicans this complex comprises of six different subunits Gpi1, Gpi2, Gpi3, Gpi15, Gpi19, and Eri1. Gpi3 is the catalytic subunit and Gpi15 is the accessory subunit which helps in catalyzing the reaction. newline This study aims to characterize the subunit Gpi15 and its interaction with two other subunits of the GPI GnT complex Gpi19 and Gpi2.Single allele deletion of GPI15 was done using PCR mediated strategy to make GPI15 heterozygote.GPI15 conditional null was also made using the same PCR strategy. As reported from our laboratory Gpi19 regulates Erg11 while Gpi2 regulates RAS signaling and Gpi19 and Gpi2 negatively regulate each other. Similar study was done in single and double mutant of GPI19 and GPI2 in GPI15 heterozygote. newline GPI15 heterozygote shows the phenotypes of both GPI19 and GPI2. It is sensitive to azoles and hypofilamentous. These phenotypic effects are enhanced in the double heterozygote of GPI19 and GPI2 but are reverted by the overexpression of GPI19 and GPI2 in GPI15 heterozygote. newline From the study it is concluded that Gpi15 cross talks with Gpi19 and Gpi2 and affects the cellular environment. This interaction shows that Gpi15 can act as a good antifungal target. newline newline