HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 24, 23408-23415, June 17, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/24/23408    most recent M502162200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bates, S. Articles by Gow, N. A. R. Search for Related Content PubMed PubMed Citation Articles by Bates, S. Articles by Gow, N. A. R. Social Bookmarking                      What's this?

Candida albicans Pmr1p, a Secretory Pathway P-type Ca²⁺/Mn²⁺-ATPase, Is Required for Glycosylation and Virulence^*

Steven Bates, Donna M. MacCallum, Gwyneth Bertram, Carol A. Munro, H. Bleddyn Hughes, Ed T. Buurman, Alistair J. P. Brown, Frank C. Odds, and Neil A. R. Gow

From the School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, United Kingdom

The cell surface of Candida albicans is the immediate point of contact with the host. The outer layer of the cell wall is enriched in highly glycosylated mannoproteins that are implicated in many aspects of the host-fungus interaction. Glycosylation of cell wall proteins is initiated in the endoplasmic reticulum and then elaborated in the Golgi as the protein passes through the secretory pathway. Golgi-bound mannosyltransferases require Mn²⁺ as an essential cofactor. In Saccharomyces cerevisiae, the P-type ATPase Pmr1p transports Ca²⁺ and Mn²⁺ ions into the Golgi. To determine the effect of a gross defect in glycosylation on host-fungus interactions of C. albicans, we disrupted the PMR1 homolog, CaPMR1. This mutation would simultaneously inhibit many Golgi-located, Mn²⁺-dependent mannosyltransferases. The Capmr1 null mutant was viable in vitro and had no growth defect even on media containing low Ca²⁺/Mn²⁺ ion concentrations. However, cells grown in these media progressively lost viability upon entering stationary phase. Phosphomannan was almost completely absent, and O-mannan was severely truncated in the null mutant. A defect in N-linked outer chain glycosylation was also apparent, demonstrated by the underglycosylation of surface acid phosphatase. Consistent with the glycosylation defect, the null mutant had a weakened cell wall, exemplified by hypersensitivity to Calcofluor white, Congo red, and hygromycin B and constitutive activation of the cell integrity pathway. In a murine model of systemic infection, the null mutant was severely attenuated in virulence. These results demonstrate the importance of glycosylation for cell wall structure and virulence of C. albicans.

Received for publication, February 25, 2005 , and in revised form, April 20, 2005.

^* This work was supported by Wellcome Trust Grants 063204 and 72263. 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.

Present address: AstraZeneca R&D Boston, Waltham, MA 02451.

To whom correspondence should be addressed. Tel.: 44-1224-555-879; Fax: 44-1224-555-844; E-mail: n.gow{at}abdn.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Miyazato, K. Nakamura, N. Yamamoto, H. M. Mora-Montes, M. Tanaka, Y. Abe, D. Tanno, K. Inden, X. Gang, K. Ishii, et al. Toll-Like Receptor 9-Dependent Activation of Myeloid Dendritic Cells by Deoxynucleic Acids from Candida albicans Infect. Immun., July 1, 2009; 77(7): 3056 - 3064. [Abstract] [Full Text] [PDF]

				M. Harris, H. M. Mora-Montes, N. A. R. Gow, and P. J. Coote 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, April 1, 2009; 155(4): 1058 - 1070. [Abstract] [Full Text] [PDF]

				A. Cambi, M. G. Netea, H. M. Mora-Montes, N. A. R. Gow, S. V. Hato, D. W. Lowman, B.-J. Kullberg, R. Torensma, D. L. Williams, and C. G. Figdor Dendritic Cell Interaction with Candida albicans Critically Depends on N-Linked Mannan J. Biol. Chem., July 18, 2008; 283(29): 20590 - 20599. [Abstract] [Full Text] [PDF]

				H. M. Mora-Montes, S. Bates, M. G. Netea, D. F. Diaz-Jimenez, E. Lopez-Romero, S. Zinker, P. Ponce-Noyola, B. J. Kullberg, A. J. P. Brown, F. C. Odds, et al. Endoplasmic Reticulum {alpha}-Glycosidases of Candida albicans Are Required for N Glycosylation, Cell Wall Integrity, and Normal Host-Fungus Interaction Eukaryot. Cell, December 1, 2007; 6(12): 2184 - 2193. [Abstract] [Full Text] [PDF]

				S. Bates, J. M. de la Rosa, D. M. MacCallum, A. J. P. Brown, N. A. R. Gow, and F. C. Odds Candida albicans Iff11, a Secreted Protein Required for Cell Wall Structure and Virulence Infect. Immun., June 1, 2007; 75(6): 2922 - 2928. [Abstract] [Full Text] [PDF]

				M. Miyatake, T. Kuno, A. Kita, K. Katsura, K. Takegawa, S. Uno, T. Nabata, and R. Sugiura Valproic Acid Affects Membrane Trafficking and Cell-Wall Integrity in Fission Yeast Genetics, April 1, 2007; 175(4): 1695 - 1705. [Abstract] [Full Text] [PDF]

				T. W. Hill, D. M. Loprete, M. Momany, Y. Ha, L. M. Harsch, J. A. Livesay, A. Mirchandani, J. J. Murdock, M. J. Vaughan, and M. B. Watt Isolation of cell wall mutants in Aspergillus nidulans by screening for hypersensitivity to Calcofluor White. Mycologia, May 1, 2006; 98(3): 399 - 409. [Abstract] [Full Text] [PDF]

				R. A. Monge, E. Roman, C. Nombela, and J. Pla The MAP kinase signal transduction network in Candida albicans. Microbiology, April 1, 2006; 152(Pt 4): 905 - 912. [Abstract] [Full Text] [PDF]

				C. Bai, X.-L. Xu, F.-Y. Chan, R. T. H. Lee, and Y. Wang MNN5 Encodes an Iron-Regulated {alpha}-1,2-Mannosyltransferase Important for Protein Glycosylation, Cell Wall Integrity, Morphogenesis, and Virulence in Candida albicans Eukaryot. Cell, February 1, 2006; 5(2): 238 - 247. [Abstract] [Full Text] [PDF]

				S. Bates, H. B. Hughes, C. A. Munro, W. P. H. Thomas, D. M. MacCallum, G. Bertram, A. Atrih, M. A. J. Ferguson, A. J. P. Brown, F. C. Odds, et al. Outer Chain N-Glycans Are Required for Cell Wall Integrity and Virulence of Candida albicans J. Biol. Chem., January 6, 2006; 281(1): 90 - 98. [Abstract] [Full Text] [PDF]

				M. Cornet, F. Bidard, P. Schwarz, G. Da Costa, S. Blanchin-Roland, F. Dromer, and C. Gaillardin Deletions of Endocytic Components VPS28 and VPS32 Affect Growth at Alkaline pH and Virulence through both RIM101-Dependent and RIM101-Independent Pathways in Candida albicans Infect. Immun., December 1, 2005; 73(12): 7977 - 7987. [Abstract] [Full Text] [PDF]