Functional analysis of Candida albicans GPI-anchored proteins: Roles in cell wall integrity and caspofungin sensitivity

Armel Plaine, Louise Walker, Gregory Da Costa, Hector M. Mora-Montes, Alastair McKinnon, Neil A. R. Gow, Claude Gaillardin, Carol A. Munro, Mathias L. Richard

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

The outer layer of the Candida albicans cell wall is enriched in highly glycosylated proteins. The major class, the GlycosylPhosphatidylInositol (GPI)-anchored proteins are tethered to the wall by GPI-anchor remnants and include adhesins, glycosyltransferases, yapsins and superoxide dismutases. In silico analysis suggested that C. albicans possesses 115 putative GPI anchored proteins (GpiPs), almost twice the number reported for Saccharomyces cerevisiae. A global approach to characterise in silico predicted GpiPs has been initiated by generating a library of 45 mutants. This library was subjected to a screen for cell wall modifications by testing the cell wall integrity (SDS and Calcofluor White sensitivity) and response to caspofungin. We showed that, when caspofungin sensitivity was modified, in more than half of the cases the susceptibility can be correlated to the level of chitin and cell wall thickness: sensitive strains have low level of chitin and a thin cell wall. We also identified, for the first time, genes that when deleted lead to decreased caspofungin sensitivity: DFG5, PHR1, PGA4 and PGA62. The role of two unknown GpiPs, Pga3l and Pga62 in the cell wall structure and composition was clearly demonstrated during this study. (c) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)1404-1414
Number of pages11
JournalFungal Genetics and Biology
Volume45
Issue number10
Early online date15 Aug 2008
DOIs
Publication statusPublished - Oct 2008

Keywords

  • candida albicans
  • GPI
  • calcofluor
  • cell wall
  • surface
  • host-pathogen interactions
  • saccharomyces-cerevisiae
  • genome-wide
  • chlamydospore formation
  • defective mutants
  • gene
  • identification
  • virulence
  • yeast
  • chitin

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