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Eukaryotic Cell, December 2007, p. 2184-2193, Vol. 6, No. 12
1535-9778/07/$08.00+0     doi:10.1128/EC.00350-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Endoplasmic Reticulum {alpha}-Glycosidases of Candida albicans Are Required for N Glycosylation, Cell Wall Integrity, and Normal Host-Fungus Interaction{triangledown}

Héctor M. Mora-Montes,1,{dagger} Steven Bates,2,{ddagger} Mihai G. Netea,3 Diana F. Díaz-Jiménez,1 Everardo López-Romero,1 Samuel Zinker,4 Patricia Ponce-Noyola,1 Bart Jan Kullberg,3 Alistair J. P. Brown,2 Frank C. Odds,2 Arturo Flores-Carreón,1 and Neil A. R. Gow2*

Instituto de Investigación en Biología Experimental, Facultad de Química, Universidad de Guanajuato, Apartado Postal 187, Guanajuato, Gto. CP 36000, México,1 School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom,2 Department of Medicine, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands,3 Departamento de Genética y Biología Molecular, CINVESTAV del IPN, Apartado Postal 14-740, México, DF 07000, México4

Received 11 July 2007/ Accepted 27 September 2007

The cell surface of Candida albicans is enriched in highly glycosylated mannoproteins that are involved in the interaction with the host tissues. N glycosylation is a posttranslational modification that is initiated in the endoplasmic reticulum (ER), where the Glc3Man9GlcNAc2 N-glycan is processed by {alpha}-glucosidases I and II and {alpha}1,2-mannosidase to generate Man8GlcNAc2. This N-oligosaccharide is then elaborated in the Golgi to form N-glycans with highly branched outer chains rich in mannose. In Saccharomyces cerevisiae, CWH41, ROT2, and MNS1 encode for {alpha}-glucosidase I, {alpha}-glucosidase II catalytic subunit, and {alpha}1,2-mannosidase, respectively. We disrupted the C. albicans CWH41, ROT2, and MNS1 homologs to determine the importance of N-oligosaccharide processing on the N-glycan outer-chain elongation and the host-fungus interaction. Yeast cells of Cacwh41{Delta}, Carot2{Delta}, and Camns1{Delta} null mutants tended to aggregate, displayed reduced growth rates, had a lower content of cell wall phosphomannan and other changes in cell wall composition, underglycosylated β-N-acetylhexosaminidase, and had a constitutively activated PKC-Mkc1 cell wall integrity pathway. They were also attenuated in virulence in a murine model of systemic infection and stimulated an altered pro- and anti-inflammatory cytokine profile from human monocytes. Therefore, N-oligosaccharide processing by ER glycosidases is required for cell wall integrity and for host-fungus interactions.

* Corresponding author. Mailing address: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom. Phone: (44) 1224-555879. Fax: (44) 1224-555844. E-mail: n.gow{at}abdn.ac.uk

{triangledown} Published ahead of print on 12 October 2007.

{dagger} Present address: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, United Kingdom.

{ddagger} Present address: School of Biosciences, University of Exeter, Exeter EX4 4PS, United Kingdom.

Eukaryotic Cell, December 2007, p. 2184-2193, Vol. 6, No. 12
1535-9778/07/$08.00+0     doi:10.1128/EC.00350-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Harris, M., Mora-Montes, H. M., Gow, N. A. R., Coote, P. J. (2009). Loss of mannosylphosphate from Candida albicans cell wall proteins results in enhanced resistance to the inhibitory effect of a cationic antimicrobial peptide via reduced peptide binding to the cell surface. Microbiology 155: 1058-1070 [Abstract] [Full Text]  
  • Mora-Montes, H. M., Bader, O., Lopez-Romero, E., Zinker, S., Ponce-Noyola, P., Hube, B., Gow, N. A. R., Flores-Carreon, A. (2008). Kex2 protease converts the endoplasmic reticulum {alpha}1,2-mannosidase of Candida albicans into a soluble cytosolic form. Microbiology 154: 3782-3794 [Abstract] [Full Text]  


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