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 A. Munro, Steven Bates, Ed T. Buurman, H. Bleddyn Hughes, Donna M. MacCallum, G Bertram, Abdel Atrih, Michael A. J. Ferguson, Judith M. Bain, Alexandra Brand, Suzanne Hamilton, Caroline Westwater, Lynn M. Thomson, Alistair J. P. Brown, Frank C. Odds, Neil A. R. Gow

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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
    JournalJournal of Biological Chemistry
    Volume280
    Issue number2
    DOIs
    Publication statusPublished - 2005

    Cite this

    Munro, C. A., Bates, S., Buurman, E. T., Hughes, H. B., MacCallum, D. M., Bertram, G., Atrih, A., Ferguson, M. A. J., Bain, J. M., Brand, A., Hamilton, S., Westwater, C., Thomson, L. M., Brown, A. J. P., Odds, F. C., & Gow, N. A. R. (2005). 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. Journal of Biological Chemistry, 280(2), 1051-1060. https://doi.org/10.1074/jbc.M411413200