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

Steven Bates*, Rebecca A. Hall, Jill Cheetham, Mihai G. Netea, Donna M. Maccallum, Alistair J. P. Brown, Frank C. Odds, Neil A. R. Gow

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Citations (Scopus)
6 Downloads (Pure)

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 α-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 vitr o 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 Δ 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 Δ 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.
Original languageEnglish
Article number294
Pages (from-to)1-9
Number of pages9
JournalBMC Research Notes
Volume6
DOIs
Publication statusPublished - 26 Jul 2013

Keywords

  • Candida albicans
  • Cell wall
  • Glycosylation
  • Mannoproteins
  • MNN1
  • Virulence

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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