Dual pili post-translational modifications synergize to mediate meningococcal adherence to platelet activating factor

Freda E-C Jen1, Matthew J Warren, Benjamin L Schulz

  • 1Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.

Plos Pathogens
|May 23, 2013
PubMed

Insights

Pathogenic Neisseria pili use phosphorylcholine (ChoP) and glycans for adherence. These modifications synergize to engage the platelet activating factor receptor (PAFr) on airway cells, a key step in meningococcal infection.

Area of Science:

  • Microbiology
  • Cell Biology
  • Molecular Biology

Background:

  • Pili are critical virulence factors in pathogenic Neisseria, mediating adhesion, motility, and DNA transformation.
  • Neisseria meningitidis pili undergo various post-translational modifications, including phase-variable phosphorylcholine (ChoP) and glycan additions.

Purpose of the Study:

  • To locate phosphorylcholine (ChoP) modifications on N. meningitidis pilin.
  • To investigate how phase-variable glycans affect ChoP surface accessibility.
  • To identify the primary receptor for meningococcal adherence to human airway cells.

Main Methods:

  • Mass spectrometry to identify modifications.
  • Analysis of pilin structure and glycan variations.
  • Cell-based assays using human bronchial epithelial cells and tissues.

Main Results:

  • Two ChoP modifications were localized to the C-terminus of N. meningitidis pilin.
  • Surface accessibility of ChoP is modulated by phase-variable glycan structures.
  • Platelet activating factor receptor (PAFr) is identified as a crucial early receptor for meningococcal adherence.

Conclusions:

  • Synergy between pilin-linked glycan and ChoP modifications is essential for optimal engagement of PAFr.
  • This interaction mediates meningococcal adherence to human airway cells, highlighting a key step in pathogenesis.

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