West, L., Lowman, D.W., Mora-Montes, H.M. et al. (6 more authors) (2013) Differential virulence of Candida glabrata glycosylation mutants. Journal of Biological Chemistry, 288 (30). 22006. ISSN 0021-9258
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. The following article is available under Author Choice. Creative Commons Attribution Unported License applies to Author Choice Articles. (http://creativecommons.org/licenses/by/3.0/). |
Keywords: | Candida albicans; Cell Wall; Fungi; Host-Pathogen Interactions; Virulence Factors |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Funding Information: | Funder Grant number NATIONAL INSTITUTES OF HEALTH - UNITED STATES OF AMERICA 5R21 AI065549-02 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Oct 2020 11:31 |
Last Modified: | 26 Oct 2020 22:06 |
Status: | Published |
Publisher: | American Society for Biochemistry and Molecular Biology |
Refereed: | Yes |
Identification Number: | 10.1074/jbc.M113.478743 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167105 |
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