Glucosamine Found as a Substituent of Both Phosphate Groups in Bordetella Lipid A Backbones: Role of a BvgAS-activated ArnT Ortholog

J Bacteriol. 2008 Jun;190(12):4281-90. doi: 10.1128/JB.01875-07. Epub 2008 Apr 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Bordetella bronchiseptica / genetics
  • Bordetella bronchiseptica / metabolism*
  • Chromatography, Gas
  • Chromatography, Thin Layer
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism
  • Glucosamine / chemistry
  • Glucosamine / metabolism*
  • Lipid A / chemistry
  • Lipid A / metabolism*
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / metabolism
  • Models, Molecular
  • Molecular Structure
  • Phosphorylation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Amino Acids
  • Fatty Acids
  • Lipid A
  • Lipopolysaccharides
  • Glucosamine