Affiliation:
1. Institute of Molecular and Cell Biology, ASTAR Biomedical Sciences Institutes, 61 Biopolis Drive, Singapore 138673, Singapore
Abstract
ABSTRACT
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
α-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 α-1,2- and α-1,6-mannobiose, and this activity requires Mn
2+
as a cofactor and is regulated by the Fe
2+
concentration. An
mnn5Δ
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
mnn5Δ
mutant also exhibited some unique defects, such as impaired hyphal growth on solid media and attenuated virulence in mice. An unanticipated phenotype was the
mnn5Δ
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.
Publisher
American Society for Microbiology
Subject
Molecular Biology,General Medicine,Microbiology
Reference57 articles.
1. Bai, C., F. Y. Chan, and Y. Wang. 2005. Identification and functional characterization of a novel Candida albicans gene CaMNN5 that suppresses the iron-dependent growth defect of Saccharomyces cerevisiae aft1Δ mutant. Biochem. J.389:27-35.
2. Bates, S., D. M. Maccallum, G. Bertram, C. A. Munro, H. B. Hughes, E. T. Buurman, A. J. Brown, F. C. Odds, and N. A. Gow. 2005. Candida albicans Pmr1p, a secretory pathway P-type Ca2+/Mn2+-ATPase, is required for glycosylation and virulence. J. Biol. Chem.280:23408-23415.
3. Beck-Sague, C., and W. R. Jarvis. 1993. Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. National Nosocomial Infections Surveillance System. J. Infect. Dis.167:1247-1251.
4. Bockmuhl, D. P., S. Krishnamurthy, M. Gerads, A. Sonneborn, and J. F. Ernst. 2001. Distinct and redundant roles of the two protein kinase A isoforms Tpk1p and Tpk2p in morphogenesis and growth of Candida albicans. Mol. Microbiol.42:1243-1257.
5. Brock, J. 1995. Lactoferrin: a multifunctional immunoregulatory protein? Immunol. Today16:417-419.
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