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

May 19th, 2014 by Hanuszkiewicz, A., Pittock, P., Humphries, F., Moll, H., Roa Rosales, A., Molinaro, A., Moynagh, P. N., Lajoie, G., Valvano, M. A.

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 ten different sites with a single sugar, 4,6-dideoxy-4-(3-hydroxybutanoylamino)-D-glucose [D-Qui4N(3HOBut)]. 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 non-glycosylated purified flagellin and a cell reporter system to assess TLR5-mediated responses, we also show that the presence of glycan in flagellin significantly impair 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.
  • Posted in Journal of Biological Chemistry, Publications
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