title: Dual pili post-translational modifications synergize to mediate meningococcal adherence to platelet activating factor receptor on human airway cells.
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.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Freda E-C
authors.initials: FE
authors.lastname: Jen
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Warren
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Schulz
authors.forename: Peter M
authors.initials: PM
authors.lastname: Power
authors.forename: W Edward
authors.initials: WE
authors.lastname: Swords
authors.forename: Jeffery N
authors.initials: JN
authors.lastname: Weiser
authors.forename: Michael A
authors.initials: MA
authors.lastname: Apicella
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Edwards
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
mesh_terms: D001422:Bacterial Adhesion; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism* / Q000382:microbiology; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D010767:Phosphorylcholine / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000382:microbiology
chemical_list: D010767:Phosphorylcholine; D036781:Fimbriae Proteins