title: Glucosamine found as a substituent of both phosphate groups in Bordetella lipid A backbones: role of a BvgAS-activated ArnT ortholog.
abstract: Endotoxins are amphipathic lipopolysaccharides (LPSs), major constituents of the outer membrane of gram-negative bacteria. They consist of a lipid region, covalently linked to a core oligosaccharide, to which may be linked a repetitive glycosidic chain carrying antigenic determinants. Most of the biological activities of endotoxins have been associated with the lipid moiety of the molecule: unique to gram-negative bacteria, LPS is a ligand of the mammalian TLR4-MD2-CD14 pathogen recognition receptor complex. Lipid A preparations are often heterogeneous with respect to both the numbers and the lengths of fatty acids and the natures of substituents on the phosphate groups when present. The variants can significantly affect host immune responses. Nine species in the Bordetella genus have been described, and the fine LPS structures of seven of them have been published. In this report, lipids A from Bordetella pertussis Tohama I and B. bronchiseptica strain 4650 were further characterized and revealed to have a glucosamine substituting both lipid A phosphate groups of the diglucosamine backbone. These substitutions have not been previously described for bordetellae. Moreover, a B. pertussis transposon mutation that maps within a gene encoding a Bordetella ArnT (formerly PmrK) glycosyl transferase ortholog does not carry this substitution, thus providing a genetic basis for the modification. Reverse transcriptase PCR of this locus showed that it is Bvg regulated, suggesting that the ability of Bordetella to modify lipid A via this glucosamine modification is a potential virulence trait.
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: Nico
authors.initials: N
authors.lastname: Marr
authors.forename: Alina
authors.initials: A
authors.lastname: Tirsoaga
authors.forename: Didier
authors.initials: D
authors.lastname: Blanot
authors.forename: Rachel
authors.initials: R
authors.lastname: Fernandez
authors.forename: Martine
authors.initials: M
authors.lastname: Caroff
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D016950:Bordetella bronchiseptica / Q000235:genetics / Q000378:metabolism*; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005944:Glucosamine / Q000737:chemistry / Q000378:metabolism*; D008050:Lipid A / Q000737:chemistry / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000596:Amino Acids; D005227:Fatty Acids; D008050:Lipid A; D008070:Lipopolysaccharides; D005944:Glucosamine