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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


    Hanuszkiewicz, Anna and Pittock, Paula and Humphries, Fiachra and Moll, Hermann and Rosales, Amanda Roa and Molinaro, Antonio and Moynagh, Paul N. and Lajoie, Gilles A. and Valvona, Miguel A. (2014) Identification of the Flagellin Glycosylation System in Burkholderia cenocepacia and the Contribution of Glycosylated Flagellin to Evasion of Human Innate Immune Responses. Journal of Biological Chemistry, 289 (27). pp. 19231-19244. ISSN 0021-9258

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    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.

    Item Type: Article
    Keywords: flagellin glycosylation; Burkholderia cenocepacia; inflammatory response; epithelial cells; Human Innate Immune Responses;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11031
    Identification Number: https://doi.org/10.1074/jbc.M114.562603
    Depositing User: Professor Paul Moynagh
    Date Deposited: 10 Sep 2019 15:28
    Journal or Publication Title: Journal of Biological Chemistry
    Publisher: American Society for Biochemistry and Molecular Biology
    Refereed: Yes
    URI:

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