Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: pertussis (whooping cough) [ICD11:
1C12.Z 
, ICD11:
XN9W3 ];
infection due to Bordetella pertussis [ICD11:
XN23B ]
The structure was elucidated in this paperNCBI PubMed ID: 20176798Publication DOI: 10.1128/IAI.01346-09Journal NLM ID: 0246127Publisher: American Society for Microbiology
Correspondence: rachelf
interchange.ubc.ca
Institutions: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada, Department of Medicine, University of Washington, Seattle, Washington, and Equipe Structure et Activite´s des Endotoxines, UMR 8621 du Centre National de la Recherche Scientifique, IGM, Universite´ de Paris-Sud-XI, Orsay, France
Bordetella pertussis endotoxin is a key modulator of the host immune response, mainly due to the role of its lipid A moiety in Toll-like receptor 4 (TLR4)-mediated signaling. We have previously demonstrated that the lipid A phosphate groups of B. pertussis BP338 can be substituted with glucosamine in a BvgAS-regulated manner. Here we examined the effect of this lipid A modification on the biological activity of B. pertussis endotoxin. We compared purified endotoxin and heat-killed B. pertussis BP338 whole cells that have modified lipid A phosphate groups to an isogenic mutant lacking this modification with respect to their capacities to induce the release of inflammatory cytokines by human and murine macrophages and to participate in the TLR4-mediated activation of NF-kappaB in transfected HEK-293 cells. We found inactivated B. pertussis cells to be stronger inducers of proinflammatory cytokines in THP-1-derived macrophages when lipid A was modified. Most notably, lack of lipid A modification abolished the ability of purified B. pertussis endotoxin to induce the release of inflammatory cytokines by human THP-1-derived macrophages but led to only slightly reduced inflammatory cytokine levels when stimulating murine (RAW 264.7) macrophages. Accordingly, upon stimulation of HEK-293 cells with inactivated bacteria and purified endotoxin, lack of lipid A modification led to impaired NF-kappaB activation only when human, and not when murine, TLR4-MD-2-CD14 was expressed. We speculate that in B. pertussis, lipid A modification has evolved to benefit the bacteria during human infection by modulating immune defenses rather than to evade innate immune recognition.
lipid A, Bordetella pertussis, cytokines, macrophages, NF-kappa B
Structure type: oligomer
Location inside paper: p.2063, fig.1E
Compound class: lipid A
Contained glycoepitopes: IEDB_141807,IEDB_151531,IEDB_176772
Methods: SDS-PAGE, MALDI-MS, genetic methods, statistical analysis
Biological activity: biological activity data of endotoxin
Biosynthesis and genetic data: genetic data
Related record ID(s): 26114, 26115
NCBI Taxonomy refs (TaxIDs): 520
Show glycosyltransferases
There is only one chemically distinct structure:
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