Differential virulence of Candida glabrata glycosylation mutants

Lara West, Douglas W Lowman, Hector M Mora-Montes, Sarah Grubb, Craig Murdoch, Martin H Thornhill, Neil A R Gow, David Williams, Ken Haynes*

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Citations (Scopus)
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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.

Original languageEnglish
Article number22006
Number of pages13
JournalThe Journal of Biological Chemistry
Volume288
Issue number30
DOIs
Publication statusPublished - 26 Jul 2013

Keywords

  • Candida albicans
  • cell wall
  • fungi
  • host-pathogen interactions
  • virulence factors
  • cell-wall mannan
  • wild-type levels
  • mannosyltransferase gene family
  • saccharomyces-cerevisiae
  • cryptococcus-neoformans
  • outer chain
  • protein glycosylation
  • pattern-recognition
  • immune recognition
  • Albicans serotype

Cite this

West, L., Lowman, D. W., Mora-Montes, H. M., Grubb, S., Murdoch, C., Thornhill, M. H., Gow, N. A. R., Williams, D., & Haynes, K. (2013). Differential virulence of Candida glabrata glycosylation mutants. The Journal of Biological Chemistry, 288(30), [22006]. https://doi.org/10.1074/jbc.M113.478743