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.
Bibliographical noteFree via Open Access: OA
Free via Creative Commons: CC
We are grateful to Xinfu Shi for technical support.
R21 AI065549-01A1RO1GM53522National Institutes of Health
Supported by National Institutes of Health Grant R21 AI065549-01A1 from NIAID (to M. H. T.).
This work was supported, in whole or in part, by National Institutes of Health Grant RO1GM53522 from NIGMS (to D. L. W.). This work was also supported by Biotechnology and Biological Sciences Research Council Grant BBF005210 (to the Haynes Laboratory), Wellcome Trust Grants 072420 075174, and Wellcome Trust Grant 080088 (to the Gow Laboratory).
- Candida albicans
- cell wall
- host-pathogen interactions
- virulence factors
- cell-wall mannan
- wild-type levels
- mannosyltransferase gene family
- outer chain
- protein glycosylation
- immune recognition
- Albicans serotype