Variability in the lipooligosaccharide structure and endotoxicity among Bordetella pertussis strains.
Bordetella endotoxins show remarkable structural variability both among each other and in comparison to other gram-negative bacteria. Here we demonstrate that, in contrast to the common Bordetella pertussis laboratory strain and Tohama I derivative BP338, lipooligosaccharide from mouse challenge strain 18-323 is a poor inducer of inflammatory cytokines in human and murine macrophages, is greatly impaired in Toll-like receptor 4-mediated activation of nuclear factor-κB in transfected HEK-293 cells, and functions as a Toll-like receptor 4 antagonist. Comparison of lipid A and lipooligosaccharide structures of B. pertussis strains BP338 and 18-323 revealed that 18-323 (1) lacks the ability to modify its lipid A phosphate groups with glucosamine, (2) is distinct in its acylation at the C3' position of the lipid A diglucosamine backbone, and (3) expresses molecular lipooligosaccharide species that lack a terminal heptose. Our findings have important implications for interpreting previous studies of host defenses to B. pertussis infection in mice and in vitro.
Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Nico
N
Marr
Alexey
A
Novikov
Adeline M
AM
Hajjar
Martine
M
Caroff
Rachel C
RC
Fernandez
D000818:Animals; D001886:Bordetella pertussis / Q000737:chemistry* / Q000472:pathogenicity; D002460:Cell Line; D004731:Endotoxins / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D051193:Toll-Like Receptors / Q000187:drug effects
D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051193:Toll-Like Receptors; C023023:lipid-linked oligosaccharides