Purification and characterization of deacylated and/or palmitoylated lipid A species unique to Salmonella enterica serovar Typhimurium

J Endotoxin Res. 2005;11(1):57-61. doi: 10.1179/096805105225006696.

Abstract

The Salmonella enterica serovar Typhimurium virulence gene products PhoP/PhoQ sense host microenvironments to regulate the expression of a lipid A 3-O-deacylase, PagL, and a lipid A palmitoyltransferase, PagP. Therefore, deacylation and/or palmitoylation of lipid A could occur in Salmonellae adapted to host environments. The PhoP/PhoQ-regulated modification of lipid A alters host recognition and signaling, and may play an important role in host defense against Salmonellae infection. Here we report the purification and characterization of modified lipid A species. Deacylated lipid A, deacylated and palmitoylated lipid A, and palmitoylated lipid A species were generated in Escherichia coli cells heterologously expressing salmonellae PagL and/or PagP, and then purified by sequential thin-layer chromatography. The purified lipid A species showed m/z values that correspond to single lipid A species on mass spectrometry analysis. The modified lipid A species showed reduced ability to induce cellular signaling through Toll-like receptor 4, suggesting a specific function of the lipid A modifications in the pathogenesis of salmonellae infection.

Publication types

  • Comparative Study

MeSH terms

  • Acylation*
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • Cell Line
  • Chromatography, Thin Layer
  • Dose-Response Relationship, Drug
  • Epitopes
  • Escherichia coli / genetics
  • Genes, Reporter
  • Humans
  • Lipid A / analysis
  • Lipid A / chemistry*
  • Lipid A / isolation & purification*
  • Lipid A / pharmacology
  • Luciferases / metabolism
  • Mass Spectrometry
  • Mice
  • Molecular Structure
  • Palmitic Acid / chemistry*
  • Plasmids
  • Polymerase Chain Reaction
  • Salmonella typhimurium / chemistry*
  • Salmonella typhimurium / classification
  • Serotyping

Substances

  • Epitopes
  • Lipid A
  • Palmitic Acid
  • Luciferases