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Papers In Press, published online ahead of print November 1, 2005
J. Biol. Chem, 10.1074/jbc.M510360200
Submitted on September 21, 2005
Revised on November 1, 2005
Accepted on November 1, 2005

Outer chain N-glycans are required for cell wall integrity and virulence of candida albicans

Steven Bates, H. Bleddyn Hughes, Carol A. Munro, William P. H. Thomas, Donna M. MacCallum, Gwyneth Bertram, Abdelmadjid Atrih, Michael A. J. Ferguson, Alistair J. P. Brown, Frank C. Odds, and Neil A. R. Gow

School of Medical Sciences, University of Aberdeen, Institute of Medical Science, Aberdeen, Scotland AB25 2ZD

Corresponding Author: n.gow{at}abdn.ac.uk

The outer layer of the Candida albicans cell wall is enriched in highly glycosylated mannoproteins that are the immediate point of contact with the host and strongly influence the host-fungal interaction. N-glycans are the major form of mannoprotein modification and consist of a core structure, common to all eukaryotes, that is further elaborated in the Golgi to form the highly branched outer chain that is characteristic of fungi. In yeasts outer chain branching is initiated by the action of the alpha 1,6-mannosyltransferase Och1p, therefore we disrupted the C. albicans OCH1 homolog to determine the importance of outer chain N-glycans on the host-fungal interaction. Loss of CaOCH1 resulted in a temperature-sensitive growth defect and cellular aggregation. Outer chain elongation of N-glycans was absent in the null mutant, demonstrated by the lack of the alpha 1,6-linked polymannose backbone and the underglycosylation of N-acetylglucosaminidase. A null mutant lacking OCH1 was hypersensitive to a range of cell wall perturbing agents and had a constitutively activated cell wall integrity pathway. These mutants had near normal growth rates in vitro but were attenuated in virulence in a murine model of systemic infection. However, tissue burdens for the Caoch1D null mutant were similar to control strains with normal N-glycosylation suggesting the host-fungal interaction was altered such that high burdens were tolerated. This demonstrates the importance of N-glycan outer chain epitopes to the host-fungal interaction and virulence.


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