Dual pili post-translational modifications synergize to mediate meningococcal adherence to platelet activating factor receptor on human airway cells

• Published in: PLoS pathogens Vol. 9; no. 5; p. e1003377
• Main Authors: Jen, Freda E-C, Warren, Matthew J, Schulz, Benjamin L, Power, Peter M, Swords, W Edward, Weiser, Jeffery N, Apicella, Michael A, Edwards, Jennifer L, Jennings, Michael P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-05-2013; Public Library of Science (PLoS)
• Subjects: Airway (Medicine); Bacterial Adhesion; Biosynthesis; Cell adhesion; Cell Lineage; Cell Membrane - metabolism; Cell Membrane - microbiology; DNA sequencing; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Fimbriae Proteins - genetics; Fimbriae Proteins - metabolism; Fimbriae, Bacterial - genetics; Fimbriae, Bacterial - metabolism; Gene expression; Genetic aspects; Health aspects; Humans; Medicine; Meningitis; Microbiology; Motility; Neisseria meningitidis - genetics; Neisseria meningitidis - metabolism; Neisseria meningitidis - pathogenicity; Neisseriaceae; Nucleotide sequencing; Phosphorylcholine - metabolism; Physiological aspects; Post-translational modification; Protein Processing, Post-Translational; Proteins; Respiratory Mucosa - metabolism; Respiratory Mucosa - microbiology; Streptococcus infections; United States; Bacterial Adhesion; Cell Lineage; Cell Membrane; Fimbriae Proteins; Fimbriae, Bacterial; Humans; Respiratory Mucosa; Epithelial Cells; Neisseria meningitidis; Protein Processing, Post-Translational; Phosphorylcholine
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003377

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.