Differential virulence of Candida glabrata glycosylation mutants.
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
© 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License applies to Author Choice Articles
The fungus Candida glabrata is an important and increasingly common pathogen of humans, particularly in immunocompromised hosts. Despite this, little is known about the attributes that allow this organism to cause disease or its interaction with the host immune system. However, in common with other fungi, the cell wall of C. glabrata is the initial point of contact between the host and pathogen, and as such, it is likely to play an important role in mediating interactions and hence virulence. Here, we show both through genetic complementation and polysaccharide structural analyses that C. glabrata ANP1, MNN2, and MNN11 encode functional orthologues of the respective Saccharomyces cerevisiae mannosyltransferases. Furthermore, we show that deletion of the C. glabrata Anp1, Mnn2, and Mnn11 mannosyltransferases directly affects the structure of the fungal N-linked mannan, in line with their predicted functions, and this has implications for cell wall integrity and consequently virulence. C. glabrata anp1 and mnn2 mutants showed increased virulence, compared with wild-type (and mnn11) cells. This is in contrast to Candida albicans where inactivation of genes involved in mannan biosynthesis has usually been linked to an attenuation of virulence. In the long term, a better understanding of the attributes that allow C. glabrata to cause disease will provide insights that can be adopted for the development of novel therapeutic and diagnostic approaches.
notes: PMCID: PMC3724654
types: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
This is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.
This research was originally published in THE JOURNAL OF BIOLOGICAL CHEMISTRY. 2013. VOL. 288, NO. 30, pp. 22006–22018, © the American Society for Biochemistry and Molecular Biology
Vol. 288, Issue 30, pp. 22006 - 22018
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