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Identification of the flagellin glycosylation system in Burkholderia cenocepacia and the contribution of glycosylated flagellin to evasion of human innate immune responses.

Abstract
Burkholderia cenocepacia is an opportunistic pathogen threatening patients with cystic fibrosis. Flagella are required for biofilm formation, as well as adhesion to and invasion of epithelial cells. Recognition of flagellin via the Toll-like receptor 5 (TLR5) contributes to exacerbate B. cenocepacia-induced lung epithelial inflammatory responses. In this study, we report that B. cenocepacia flagellin is glycosylated on at least 10 different sites with a single sugar, 4,6-dideoxy-4-(3-hydroxybutanoylamino)-D-glucose. We have identified key genes that are required for flagellin glycosylation, including a predicted glycosyltransferase gene that is linked to the flagellin biosynthesis cluster and a putative acetyltransferase gene located within the O-antigen lipopolysaccharide cluster. Another O-antigen cluster gene, rmlB, which is required for flagellin glycan and O-antigen biosynthesis, was essential for bacterial viability, uncovering a novel target against Burkholderia infections. Using glycosylated and nonglycosylated purified flagellin and a cell reporter system to assess TLR5-mediated responses, we also show that the presence of glycan in flagellin significantly impairs the inflammatory response of epithelial cells. We therefore suggest that flagellin glycosylation reduces recognition of flagellin by host TLR5, providing an evasive strategy to infecting bacteria.
AuthorsAnna Hanuszkiewicz, Paula Pittock, Fiachra Humphries, Hermann Moll, Amanda Roa Rosales, Antonio Molinaro, Paul N Moynagh, Gilles A Lajoie, Miguel A Valvano
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 27 Pg. 19231-44 (Jul 04 2014) ISSN: 1083-351X [Electronic] United States
PMID24841205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Chemical References
  • Toll-Like Receptor 5
  • Flagellin
  • Glucose
Topics
  • Amino Acid Sequence
  • Biofilms (growth & development)
  • Burkholderia cenocepacia (genetics, immunology, metabolism, physiology)
  • Cell Line
  • Epithelial Cells (immunology, microbiology)
  • Flagellin (chemistry, genetics, immunology, metabolism)
  • Glucose (chemistry, metabolism)
  • Glycosylation
  • Humans
  • Immunity, Innate
  • Molecular Sequence Data
  • Movement
  • Toll-Like Receptor 5 (metabolism)

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