The Candida albicans homologue of PIG-P, CaGpi19p: gene dosage and role in growth and filamentation.
Glycosylphosphatidyl inositol (GPI)-anchored proteins in Candida albicans are responsible for a vast range of functions, and deletions in certain GPI-anchored proteins severely reduce adhesion and virulence of this organism. In addition, completely modified GPIs are necessary for virulence. GPI anchor biosynthesis is essential for viability and starts with the transfer of N-acetylglucosamine to phosphatidylinositol. This step is catalysed by a multi-subunit complex, GPI-N-acetylglucosaminyltransferase (GPI-GnT). In this, the first report to our knowledge on a subunit of the Candida GPI-GnT complex, we show that CaGpi19p is the functional equivalent of the Saccharomyces cerevisiae Gpi19p. An N-terminal truncation mutant of CaGpi19p functionally complements a conditionally lethal S. cerevisiae gpi19 mutant. Further, we constructed a conditional null mutant of CaGPI19 by disrupting one allele and placing the remaining copy under the control of the MET3 promoter. Repression leads to growth defects, cell wall biogenesis aberrations, azole sensitivity and hyperfilamention. In addition, there is a noticeable gene dosage effect, with the heterozygote also displaying intermediate degrees of most phenotypes. The mutants also displayed a reduced susceptibility to the antifungal agent amphotericin B. Collectively, the results suggest that CaGPI19 is required for normal morphology and cell wall architecture.
Victoria
Guiliana Soraya
GS
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Kumar
Pravin
P
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Komath
Sneha Sudha
SS
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
D002176:Candida albicans / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D002473:Cell Wall / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D005816:Genetic Complementation Test; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism*; D025301:Hyphae / Q000254:growth & development; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D005964:Glucosyltransferases; C508482:Gpi19 protein, S cerevisiae