Mnt1p and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and virulence

Carol Anne Munro, Steven Bates, E T Buurman, H B Hughes, Donna Margaret MacCallum, G Bertram, A Atrih, MacNeill Alisdair Ferguson, Judith Margaret Bain, Alexandra Carolyn Brand, S Hamilton, C Westwater, Lynn Margaret Thomson, Alistair James Petersen Brown, Frank Odds, Neil Andrew Robert Gow

Research output: Contribution to journalArticle

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Abstract

The MNT1 gene of the human fungal pathogen Candida albicans is involved in O-glycosylation of cell wall and secreted proteins and is important for adherence of C. albicans to host surfaces and for virulence. Here we describe the molecular analysis of CaMNT2, a second member of the MNT1-like gene family in C. albicans. Mnt2p also functions in O-glycosylation. Mnt1p and Mnt2p encode partially redundant alpha-1,2-mannosyltransferases that catalyze the addition of the second and third mannose residues in an O-linked mannose pentamer. Deletion of both copies of MNT1 and MNT2 resulted in reduction in the level of in vitro mannosyltransferase activity and truncation of O-mannan. Both the mnt2Delta and mnt1Delta single mutants were significantly reduced in adherence to human buccal epithelial cells and Matrigel-coated surfaces, indicating a role for O-glycosylated cell wall proteins or O-mannan itself in adhesion to host surfaces. The double mnt1Deltamnt2Delta mutant formed aggregates of cells that appeared to be the result of abnormal cell separation. The double mutant was attenuated in virulence, underlining the importance of O-glycosylation in pathogenesis of C. albicans infections.

Original languageEnglish
Pages (from-to)1051-1060
Number of pages10
JournalThe Journal of Biological Chemistry
Volume280
Early online date1 Nov 2004
DOIs
Publication statusPublished - 14 Jan 2005

Keywords

  • yeast-cell-wall
  • mannosyltransferase gene family
  • buccal epithelial-cells
  • wild-type cells
  • saccharomyces-cerevisiae
  • functional-characterization
  • defective-mutant
  • pichia-pastoris
  • N-glycosylation
  • in-vitro

Cite this

Mnt1p and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and virulence. / Munro, Carol Anne; Bates, Steven; Buurman, E T ; Hughes, H B ; MacCallum, Donna Margaret; Bertram, G ; Atrih, A ; Ferguson, MacNeill Alisdair; Bain, Judith Margaret; Brand, Alexandra Carolyn; Hamilton, S; Westwater, C ; Thomson, Lynn Margaret; Brown, Alistair James Petersen; Odds, Frank; Gow, Neil Andrew Robert.

In: The Journal of Biological Chemistry, Vol. 280, 14.01.2005, p. 1051-1060.

Research output: Contribution to journalArticle

Munro, Carol Anne ; Bates, Steven ; Buurman, E T ; Hughes, H B ; MacCallum, Donna Margaret ; Bertram, G ; Atrih, A ; Ferguson, MacNeill Alisdair ; Bain, Judith Margaret ; Brand, Alexandra Carolyn ; Hamilton, S ; Westwater, C ; Thomson, Lynn Margaret ; Brown, Alistair James Petersen ; Odds, Frank ; Gow, Neil Andrew Robert. / Mnt1p and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and virulence. In: The Journal of Biological Chemistry. 2005 ; Vol. 280. pp. 1051-1060.
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abstract = "The MNT1 gene of the human fungal pathogen Candida albicans is involved in O-glycosylation of cell wall and secreted proteins and is important for adherence of C. albicans to host surfaces and for virulence. Here we describe the molecular analysis of CaMNT2, a second member of the MNT1-like gene family in C. albicans. Mnt2p also functions in O-glycosylation. Mnt1p and Mnt2p encode partially redundant alpha-1,2-mannosyltransferases that catalyze the addition of the second and third mannose residues in an O-linked mannose pentamer. Deletion of both copies of MNT1 and MNT2 resulted in reduction in the level of in vitro mannosyltransferase activity and truncation of O-mannan. Both the mnt2Delta and mnt1Delta single mutants were significantly reduced in adherence to human buccal epithelial cells and Matrigel-coated surfaces, indicating a role for O-glycosylated cell wall proteins or O-mannan itself in adhesion to host surfaces. The double mnt1Deltamnt2Delta mutant formed aggregates of cells that appeared to be the result of abnormal cell separation. The double mutant was attenuated in virulence, underlining the importance of O-glycosylation in pathogenesis of C. albicans infections.",
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T1 - Mnt1p and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and virulence

AU - Munro, Carol Anne

AU - Bates, Steven

AU - Buurman, E T

AU - Hughes, H B

AU - MacCallum, Donna Margaret

AU - Bertram, G

AU - Atrih, A

AU - Ferguson, MacNeill Alisdair

AU - Bain, Judith Margaret

AU - Brand, Alexandra Carolyn

AU - Hamilton, S

AU - Westwater, C

AU - Thomson, Lynn Margaret

AU - Brown, Alistair James Petersen

AU - Odds, Frank

AU - Gow, Neil Andrew Robert

PY - 2005/1/14

Y1 - 2005/1/14

N2 - The MNT1 gene of the human fungal pathogen Candida albicans is involved in O-glycosylation of cell wall and secreted proteins and is important for adherence of C. albicans to host surfaces and for virulence. Here we describe the molecular analysis of CaMNT2, a second member of the MNT1-like gene family in C. albicans. Mnt2p also functions in O-glycosylation. Mnt1p and Mnt2p encode partially redundant alpha-1,2-mannosyltransferases that catalyze the addition of the second and third mannose residues in an O-linked mannose pentamer. Deletion of both copies of MNT1 and MNT2 resulted in reduction in the level of in vitro mannosyltransferase activity and truncation of O-mannan. Both the mnt2Delta and mnt1Delta single mutants were significantly reduced in adherence to human buccal epithelial cells and Matrigel-coated surfaces, indicating a role for O-glycosylated cell wall proteins or O-mannan itself in adhesion to host surfaces. The double mnt1Deltamnt2Delta mutant formed aggregates of cells that appeared to be the result of abnormal cell separation. The double mutant was attenuated in virulence, underlining the importance of O-glycosylation in pathogenesis of C. albicans infections.

AB - The MNT1 gene of the human fungal pathogen Candida albicans is involved in O-glycosylation of cell wall and secreted proteins and is important for adherence of C. albicans to host surfaces and for virulence. Here we describe the molecular analysis of CaMNT2, a second member of the MNT1-like gene family in C. albicans. Mnt2p also functions in O-glycosylation. Mnt1p and Mnt2p encode partially redundant alpha-1,2-mannosyltransferases that catalyze the addition of the second and third mannose residues in an O-linked mannose pentamer. Deletion of both copies of MNT1 and MNT2 resulted in reduction in the level of in vitro mannosyltransferase activity and truncation of O-mannan. Both the mnt2Delta and mnt1Delta single mutants were significantly reduced in adherence to human buccal epithelial cells and Matrigel-coated surfaces, indicating a role for O-glycosylated cell wall proteins or O-mannan itself in adhesion to host surfaces. The double mnt1Deltamnt2Delta mutant formed aggregates of cells that appeared to be the result of abnormal cell separation. The double mutant was attenuated in virulence, underlining the importance of O-glycosylation in pathogenesis of C. albicans infections.

KW - yeast-cell-wall

KW - mannosyltransferase gene family

KW - buccal epithelial-cells

KW - wild-type cells

KW - saccharomyces-cerevisiae

KW - functional-characterization

KW - defective-mutant

KW - pichia-pastoris

KW - N-glycosylation

KW - in-vitro

U2 - 10.1074/jbc.M411413200

DO - 10.1074/jbc.M411413200

M3 - Article

VL - 280

SP - 1051

EP - 1060

JO - The Journal of Biological Chemistry

JF - The Journal of Biological Chemistry

SN - 0021-9258

ER -