Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
NCBI PubMed ID: 15659161Publication DOI: 0.1111/j.1365-2958.2004.04409.xJournal NLM ID: 8712028Publisher: Blackwell Publishing
Correspondence: raetz
biochem.duke.edu
Institutions: Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA, Department of Pharmacology and Molecular Sciences, Middle Atlantic Mass Spectrometry Laboratory, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Lipid A of Salmonella typhimurium is covalently modified with additional acyl and/or polar substituents in response to activation of the PhoP/PhoQ and/or PmrA/PmrB signalling systems, which are induced by growth at low Mg2+ concentrations and mild acid pH respectively. Although these conditions are thought to exist within macrophage phagolysosomes, no direct evidence for lipid A modification after endocytosis has been presented. To address this issue, we grew S. typhimurium inside RAW264.7 cells in the presence of 32Pi, and then isolated the labelled lipid A fraction, which was found to be extensively derivatized with phosphoethanolamine, aminoarabinose, 2-hydroxymyristate and/or palmitate moieties. S. typhimurium grown in tissue culture medium synthesized lipid A molecules lacking all these substituents with the exception of the 2-hydroxymyristate chain, which was still present. Using defined minimal media to simulate the intracellular pH and Mg2+ concentrations of endosomes, we found that lipid A of S. typhimurium grown in an acidic, low-Mg2+ medium closely resembled lipid A isolated from bacteria internalized by RAW264.7 cells. A subset of S. typhimurium lipid A modifications were induced by low Mg2+ alone. Escherichia coli K-12 W3110 modified its lipid A molecules in response to growth under acidic but not low-Mg2+ conditions. Growth in a high-Mg2+, mildly alkaline medium resulted in suppression of most lipid A modifications with the exception of the 2-hydroxymyristate in S. typhimurium. Although lpxO transcription was stimulated by growth on low Mg2+, the biosynthesis of lipid A species containing 2-hydroxymyristate was independent of PhoP/PhoQ and PmrA/PmrB in S. typhimurium. Our labelling methods should be applicable to studies of lipid A modifications induced by endocytosis of diverse bacteria.
Escherichia coli, lipid A, Salmonella typhimurium, lpxO
Structure type: oligomer
Location inside paper: p.426, fig.1A, 10mM MgCl2, pH 7.5
Compound class: lipid A
Contained glycoepitopes: IEDB_141807,IEDB_151531,IEDB_176772,IEDB_534864
Methods: TLC, MALDI-TOF MS, radiolabeling, genetic methods, radioactivity measurement, enzyme assay
Related record ID(s): 31259, 31260, 31261, 31262, 31263, 31264, 31265, 31266, 31267, 31268
NCBI Taxonomy refs (TaxIDs): 562
Show glycosyltransferases
There is only one chemically distinct structure:
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