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

16 Citations (Scopus)
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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

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Candida
Glycosylation
Candida albicans
Cell Wall
Virulence
Genes
Cells
Defects
Host-Pathogen Interactions
Mannans
Pathogens
Mannosyltransferases
Chain length
Polysaccharides
Redundancy
Epitopes
Hypersensitivity
Infection
Chemical analysis

Keywords

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

ASJC Scopus subject areas

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

Cite this

Role of the Candida albicans MNN1 gene family in cell wall structure and virulence. / Bates, Steven; Hall, Rebecca A.; Cheetham, Jill; Netea, Mihai G.; Maccallum, Donna M.; Brown, Alistair J. P.; Odds, Frank C.; Gow, Neil A. R.

In: BMC Research Notes, Vol. 6, 294, 26.07.2013, p. 1-9.

Research output: Contribution to journalArticle

Bates, Steven ; Hall, Rebecca A. ; Cheetham, Jill ; Netea, Mihai G. ; Maccallum, Donna M. ; Brown, Alistair J. P. ; Odds, Frank C. ; Gow, Neil A. R. / Role of the Candida albicans MNN1 gene family in cell wall structure and virulence. In: BMC Research Notes. 2013 ; Vol. 6. pp. 1-9.
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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.",
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note = "Acknowledgements This work was supported by a Wellcome Trust Programme grant (080088) to NG, FO and AB and by a FP7-2007-2013 grant agreement (HEALTH-F2- 2010-260338–ALLFUN) and BBSRC SABR (CRISP) award. MGN was supported by a Vici grant of the Netherlands Organization for Scientific Research. JC was supported by a UK Biotechnology and Biological Sciences Research Council project grant (BB/F009232/1) to SB.",
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AU - Bates, Steven

AU - Hall, Rebecca A.

AU - Cheetham, Jill

AU - Netea, Mihai G.

AU - Maccallum, Donna M.

AU - Brown, Alistair J. P.

AU - Odds, Frank C.

AU - Gow, Neil A. R.

N1 - Acknowledgements This work was supported by a Wellcome Trust Programme grant (080088) to NG, FO and AB and by a FP7-2007-2013 grant agreement (HEALTH-F2- 2010-260338–ALLFUN) and BBSRC SABR (CRISP) award. MGN was supported by a Vici grant of the Netherlands Organization for Scientific Research. JC was supported by a UK Biotechnology and Biological Sciences Research Council project grant (BB/F009232/1) to SB.

PY - 2013/7/26

Y1 - 2013/7/26

N2 - 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.

AB - 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.

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KW - Glycosylation

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