TY - JOUR
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
SN - 0021-9258
VL - 280
SP - 1051
EP - 1060
JO - The Journal of Biological Chemistry
JF - The Journal of Biological Chemistry
ER -