Dual Pili Post-translational Modifications Synergize to Mediate Meningococcal Adherence to Platelet Activating Factor Receptor on Human Airway Cells

PLoS Pathogens

Michael A. Apicella¹  Jeffery N. Weiser²  W. Edward Swords³  Freda E. C. Jen⁴  Michael P. Jennings⁴  Peter M. Power⁵  Benjamin L. Schulz⁶  Matthew J. Warren⁶  Jennifer L. Edwards⁷ 

[1] Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America;Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America;Department of Microbiology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America;Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia;Molecular Infectious Diseases Group, Department of Paediatrics, Weatherall Institute for Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom;School of Chemistry Molecular Biosciences, University of Queensland, St Lucia, Brisbane, Queensland, Australia;The Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital and the Department of Pediatrics, The Ohio State University, Columbus, Ohio, United States of America

关键词: Neisseria meningitidis;    Pili;    fimbriae;    Antibodies;    Immunoprecipitation;    Mutant strains;    Epithelial cells;    Glycosylation;    Post-translational modification;   

DOI  :  10.1371/journal.ppat.1003377

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY