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J. Biol. Chem., Vol. 281, Issue 1, 90-98, January 6, 2006

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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 Atrih1, Michael A. J. Ferguson1, Alistair J. P. Brown, Frank C. Odds, and Neil A. R. Gow2

From the School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD and the School of Life Sciences, Wellcome Trust Building, University of Dundee, Dundee DD1 4NH, Scotland, United Kingdom

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 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 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 Caoch1 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.

Received for publication, September 21, 2005 , and in revised form, November 1, 2005.

^* This work was supported in part by Wellcome Trust Grants 063204 and 72263 (to N. A. R. G., F. C. O., and A. J. P. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by Wellcome Trust Programme Grant 071463.

² To whom correspondence should be addressed. Tel.: 44-1224-555879; Fax: 44-1224-555844; E-mail: n.gow{at}abdn.ac.uk.

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