Role of the Candida albicans MNN1 gene family in cell wall structure and virulence

Research output: Contribution to journalArticlepeer-review

Authors

  • Steven Bates
  • Jill Cheetham
  • Mihai G Netea
  • Donna M Maccallum
  • Alister JP Brown
  • Frank C Odds
  • Neil A R Gow

Colleges, School and Institutes

External organisations

  • Univ Aberdeen
  • Univ Exeter
  • Univ Nijmegen

Abstract

Background
The Candida albicans cell wall is the first point of contact with the host, and its outer surface is heavily enriched in mannoproteins modified through the addition of N- and O-mannan. Previous work, using mutants with gross defects in glycosylation, has clearly identified the importance of mannan in the host-pathogen interaction, immune recognition and virulence. Here we report the first analysis of the MNN1 gene family, which contains six members predicted to act as alpha-1,3 mannosyltransferases in the terminal stages of glycosylation.

Findings We generated single null mutants in all members of the C. albicans MNN1 gene family, and disruption of MNN14 led to both in vitro and in vivo defects. Null mutants in other members of the family demonstrated no phenotypic defects, suggesting that these members may display functional redundancy. The mnn14[increment] null mutant displayed hypersensitivity to agents associated with cell wall and glycosylation defects, suggesting an altered cell wall structure. However, no gross changes in cell wall composition or N-glycosylation were identified in this mutant, although an extension of phosphomannan chain length was apparent. Although the cell wall defects associated with the mnn14[increment] mutant were subtle, this mutant displayed a severe attenuation of virulence in a murine infection model.

Conclusion
Mnn14 plays a distinct role from other members of the MNN1 family, demonstrating that specific N-glycan outer chain epitopes are required in the host-pathogen interaction and virulence.

Details

Original languageEnglish
Article number294
Number of pages9
JournalBMC Research Notes
Volume6
Early online date26 Jul 2013
Publication statusPublished - 26 Jul 2013

Keywords

  • Candida albicans , cell wall synthesis, Mnn1