This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bai, C. Articles by Wang, Y. Search for Related Content PubMed PubMed Citation Articles by Bai, C. Articles by Wang, Y.

 Previous Article  |  Next Article 

Eukaryotic Cell, February 2006, p. 238-247, Vol. 5, No. 2
1535-9778/06/$08.00+0     doi:10.1128/EC.5.2.238-247.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

MNN5 Encodes an Iron-Regulated -1,2-Mannosyltransferase Important for Protein Glycosylation, Cell Wall Integrity, Morphogenesis, and Virulence in Candida albicans

Chen Bai, Xiao-Li Xu, Fong-Yee Chan, Raymond Teck Ho Lee, and Yue Wang^*

Institute of Molecular and Cell Biology, ASTAR Biomedical Sciences Institutes, 61 Biopolis Drive, Singapore 138673, Singapore

Received 13 September 2005/ Accepted 23 November 2005

The cell walls of microbial pathogens mediate physical interactions with host cells and hence play a key role in infection. Mannosyltransferases have been shown to determine the cell wall properties and virulence of the pathogenic fungus Candida albicans. We previously identified a C. albicans -1,2-mannosyltransferase, Mnn5, for its novel ability to enhance iron usage in Saccharomyces cerevisiae. Here we have studied the enzymatic properties of purified Mnn5 and characterized its function in its natural host. Mnn5 catalyzes the transfer of mannose to both -1,2- and -1,6-mannobiose, and this activity requires Mn²⁺ as a cofactor and is regulated by the Fe²⁺ concentration. An mnn5 mutant showed a lowered ability to extend O-linked, and possibly also N-linked, mannans, hypersensitivity to cell wall-damaging agents, and a reduction of cell wall mannosylphosphate content, phenotypes typical of many fungal mannosyltransferase mutants. The mnn5 mutant also exhibited some unique defects, such as impaired hyphal growth on solid media and attenuated virulence in mice. An unanticipated phenotype was the mnn5 mutant's resistance to killing by the iron-chelating protein lactoferrin, rendering it the first protein found that mediates lactoferrin killing of C. albicans. In summary, MNN5 deletion impairs a wide range of cellular events, most likely due to its broad substrate specificity. Of particular interest was the observed role of iron in regulating the enzymatic activity, suggesting an underlying relationship between Mnn5 activity and cellular iron homeostasis.

---

* Corresponding author. Mailing address: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore. Phone: 65-6586-9521. Fax: 65-6779-1117. E-mail: mcbwangy{at}imcb.a-star.edu.sg.

---

Eukaryotic Cell, February 2006, p. 238-247, Vol. 5, No. 2
1535-9778/06/$08.00+0     doi:10.1128/EC.5.2.238-247.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Shibata, N., Saitoh, T., Tadokoro, Y., Okawa, Y. (2009). The cell wall galactomannan antigen from Malassezia furfur and Malassezia pachydermatis contains {beta}-1,6-linked linear galactofuranosyl residues and its detection has diagnostic potential. Microbiology 155: 3420-3429 [Abstract] [Full Text]  
• Jiang, H., Ouyang, H., Zhou, H., Jin, C. (2008). GDP-mannose pyrophosphorylase is essential for cell wall integrity, morphogenesis and viability of Aspergillus fumigatus. Microbiology 154: 2730-2739 [Abstract] [Full Text]  
• Hazen, K. C, Singleton, D. R, Masuoka, J. (2007). Influence of outer region mannosylphosphorylation on N-glycan formation by Candida albicans: Normal acid-stable N-glycan formation requires acid-labile mannosylphosphate addition. Glycobiology 17: 1052-1060 [Abstract] [Full Text]