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

doi:10.1016/j.fgb.2008.08.003

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

Medical Sciences

CNRS

Research output: Contribution to journal › Article

191 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 language	English
Pages (from-to)	1404-1414
Number of pages	11
Journal	Fungal Genetics and Biology
Volume	45
Issue number	10
Early online date	15 Aug 2008
DOIs	https://doi.org/10.1016/j.fgb.2008.08.003
Publication status	Published - Oct 2008

Bibliographical note

A paid open access option is available for this journal.
Voluntary deposit by author of pre-print allowed on Institutions open scholarly website and pre-print servers
Voluntary deposit by author of authors post-print allowed on institutions open scholarly website including Institutional Repository
Deposit due to Funding Body, Institutional and Governmental mandate only allowed where separate agreement between repository and publisher exists
Set statement to accompany deposit
Published source must be acknowledged
Must link to journal home page or articles' DOI
Publisher's version/PDF cannot be used
Articles in some journals can be made Open Access on payment of additional charge
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Authors who are required to deposit in subject-based repositories may also use Sponsorship Option

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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@article{08ab105389e14470b18d06b134c1cdb5,

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

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.",

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

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

note = "A paid open access option is available for this journal. Voluntary deposit by author of pre-print allowed on Institutions open scholarly website and pre-print servers Voluntary deposit by author of authors post-print allowed on institutions open scholarly website including Institutional Repository Deposit due to Funding Body, Institutional and Governmental mandate only allowed where separate agreement between repository and publisher exists Set statement to accompany deposit Published source must be acknowledged Must link to journal home page or articles' DOI Publisher's version/PDF cannot be used Articles in some journals can be made Open Access on payment of additional charge NIH Authors articles will be submitted to PubMed Central after 12 months Authors who are required to deposit in subject-based repositories may also use Sponsorship Option ",

year = "2008",

month = oct,

doi = "10.1016/j.fgb.2008.08.003",

language = "English",

volume = "45",

pages = "1404--1414",

journal = "Fungal Genetics and Biology",

issn = "1087-1845",

publisher = "Academic Press Inc.",

number = "10",

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T1 - Functional analysis of Candida albicans GPI-anchored proteins

T2 - Roles in cell wall integrity and caspofungin sensitivity

AU - Plaine, Armel

AU - Walker, Louise

AU - Da Costa, Gregory

AU - Mora-Montes, Hector M.

AU - McKinnon, Alastair

AU - Gow, Neil A. R.

AU - Gaillardin, Claude

AU - Munro, Carol A.

AU - Richard, Mathias L.

N1 - A paid open access option is available for this journal. Voluntary deposit by author of pre-print allowed on Institutions open scholarly website and pre-print servers Voluntary deposit by author of authors post-print allowed on institutions open scholarly website including Institutional Repository Deposit due to Funding Body, Institutional and Governmental mandate only allowed where separate agreement between repository and publisher exists Set statement to accompany deposit Published source must be acknowledged Must link to journal home page or articles' DOI Publisher's version/PDF cannot be used Articles in some journals can be made Open Access on payment of additional charge NIH Authors articles will be submitted to PubMed Central after 12 months Authors who are required to deposit in subject-based repositories may also use Sponsorship Option

PY - 2008/10

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N2 - 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.

AB - 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.

KW - candida albicans

KW - GPI

KW - calcofluor

KW - cell wall

KW - surface

KW - host-pathogen interactions

KW - saccharomyces-cerevisiae

KW - genome-wide

KW - chlamydospore formation

KW - defective mutants

KW - gene

KW - identification

KW - virulence

KW - yeast

KW - chitin

U2 - 10.1016/j.fgb.2008.08.003

DO - 10.1016/j.fgb.2008.08.003

M3 - Article

SN - 1087-1845

VL - 45

SP - 1404

EP - 1414

JO - Fungal Genetics and Biology

JF - Fungal Genetics and Biology

IS - 10

ER -

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

Abstract

Bibliographical note

Keywords

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