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.
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.
Munro
Carol A
CA
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
Bates
Steven
S
Buurman
Ed T
ET
Hughes
H Bleddyn
HB
Maccallum
Donna M
DM
Bertram
Gwyneth
G
Atrih
Abdel
A
Ferguson
Michael A J
MA
Bain
Judith M
JM
Brand
Alexandra
A
Hamilton
Suzanne
S
Westwater
Caroline
C
Thomson
Lynn M
LM
Brown
Alistair J P
AJ
Odds
Frank C
FC
Gow
Neil A R
NA
D002176:Candida albicans / Q000737:chemistry / Q000166:cytology / Q000201:enzymology* / Q000472:pathogenicity*; D002448:Cell Adhesion; D049109:Cell Proliferation; D048430:Cell Shape; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017353:Gene Deletion; D008358:Mannose / Q000378:metabolism*; D008364:Mannosyltransferases / Q000172:deficiency / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013058:Mass Spectrometry; D008745:Methylation; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry; D014774:Virulence / Q000502:physiology; D037521:Virulence Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D005656:Fungal Proteins; D011134:Polysaccharides; D037521:Virulence Factors; D008364:Mannosyltransferases; D008358:Mannose