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Published on: April 1, 2014
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.
Abstract:
Pili of pathogenic Neisseria are major virulence factors associated with adhesion, twitching motility, auto-aggregation, and DNA transformation. Pili of N. meningitidis are subject to several different post-translational modifications. Among these pilin modifications, the presence of phosphorylcholine (ChoP) and a glycan on the pilin protein are phase-variable (subject to high frequency, reversible on/off switching of expression). In this study we report the location of two ChoP modifications on the C-terminus of N. meningitidis pilin. We show that the surface accessibility of ChoP on pili is affected by phase variable changes to the structure of the pilin-linked glycan. We identify for the first time that the platelet activating factor receptor (PAFr) is a key, early event receptor for meningococcal adherence to human bronchial epithelial cells and tissue, and that synergy between the pilin-linked glycan and ChoP post-translational modifications is required for pili to optimally engage PAFr to mediate adherence to human airway cells.
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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