Neisseria meningitidis Type IV Pili Composed of Sequence Invariable Pilins Are Masked by Multisite Glycosylation

Joseph Gault, Mathias Ferber, Silke Machata, Anne Flore Imhaus, Christian Malosse, Arthur Charles-Orszag, Corinne Millien, Guillaume Bouvier, Benjamin Bardiaux, Gérard Péhau-Arnaudet, Kelly Klinge, Isabelle Podglajen, Marie Cécile Ploy, H. Steven Seifert, Michael Nilges, Julia Chamot-Rooke, Guillaume Duménil*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The ability of pathogens to cause disease depends on their aptitude to escape the immune system. Type IV pili are extracellular filamentous virulence factors composed of pilin monomers and frequently expressed by bacterial pathogens. As such they are major targets for the host immune system. In the human pathogen Neisseria meningitidis, strains expressing class I pilins contain a genetic recombination system that promotes variation of the pilin sequence and is thought to aid immune escape. However, numerous hypervirulent clinical isolates express class II pilins that lack this property. This raises the question of how they evade immunity targeting type IV pili. As glycosylation is a possible source of antigenic variation it was investigated using top-down mass spectrometry to provide the highest molecular precision on the modified proteins. Unlike class I pilins that carry a single glycan, we found that class II pilins display up to 5 glycosylation sites per monomer on the pilus surface. Swapping of pilin class and genetic background shows that the pilin primary structure determines multisite glycosylation while the genetic background determines the nature of the glycans. Absence of glycosylation in class II pilins affects pilus biogenesis or enhances pilus-dependent aggregation in a strain specific fashion highlighting the extensive functional impact of multisite glycosylation. Finally, molecular modeling shows that glycans cover the surface of class II pilins and strongly decrease antibody access to the polypeptide chain. This strongly supports a model where strains expressing class II pilins evade the immune system by changing their sugar structure rather than pilin primary structure. Overall these results show that sequence invariable class II pilins are cloaked in glycans with extensive functional and immunological consequences.

Original languageEnglish (US)
Article numbere1005162
Pages (from-to)1-24
Number of pages24
JournalPLoS pathogens
Volume11
Issue number9
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Gault, J., Ferber, M., Machata, S., Imhaus, A. F., Malosse, C., Charles-Orszag, A., Millien, C., Bouvier, G., Bardiaux, B., Péhau-Arnaudet, G., Klinge, K., Podglajen, I., Ploy, M. C., Seifert, H. S., Nilges, M., Chamot-Rooke, J., & Duménil, G. (2015). Neisseria meningitidis Type IV Pili Composed of Sequence Invariable Pilins Are Masked by Multisite Glycosylation. PLoS pathogens, 11(9), 1-24. [e1005162]. https://doi.org/10.1371/journal.ppat.1005162