ArticleThe Journal of biological chemistry2004
A methylated phosphate group and four amide-linked acyl chains in leptospira interrogans lipid A. The membrane anchor of an unusual lipopolysaccharide that activates TLR2.
Article in The Journal of biological chemistry, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Role of Toll-like receptor 2 during infection of Leptospira spp: A systematic review.PloS one · 2024Pooled it
- Randomized controlled trial of pulse methyl prednisolone × placebo in treatment of pulmonary involvement associated with severe leptospirosis. [ISRCTN74625030].BMC infectious diseases · 2011Trial
- DMEM and EMEM as alternate growth media for pathogenic Leptospira.PLoS neglected tropical diseases · 2026Article
- Purification of Lipopolysaccharides from Leptospira.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Shaping the future ofJournal of medical microbiology · 2025Review
- Roles of Gut Microbiota and Associated Metabolites inPolish journal of microbiology · 2025Article
- TLR4 competence and mouse models of sublethal leptospirosis.PLoS neglected tropical diseases · 2025Article
- DMEM and EMEM are suitable surrogate media to mimic host environment and expand leptospiral pathogenesis studies usingbioRxiv : the preprint server for biology · 2025Article
- Levels of Cytokines in Leptospirosis Patients with Different Serovars andJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2024Article
- Identification of equine mares as reservoir hosts for pathogenic species ofFrontiers in veterinary science · 2024Article
- Article
- Primary Structure of Glycans by NMR Spectroscopy.Chemical reviews · 2023Review
- Horizontal transfer of theLife science alliance · 2023Article
- Lipid A structural diversity among members of the genusFrontiers in microbiology · 2023Article
- Weil's Disease-Immunopathogenesis, Multiple Organ Failure, and Potential Role of Gut Microbiota.Biomolecules · 2022Review
- A Sensitive GC-MS Method for Quantitation of Lipid A Backbone Components and Terminal Phosphate Modifications.Journal of the American Society for Mass Spectrometry · 2022Article
- Host and Species-Specificities of Pattern Recognition Receptors Upon Infection WithFrontiers in cellular and infection microbiology · 2022Review
- Lipid A heterogeneity and its role in the host interactions with pathogenic and commensal bacteria.microLife · 2022Review
- Challenges for the development of a universal vaccine against leptospirosis revealed by the evaluation of 22 vaccine candidates.Frontiers in cellular and infection microbiology · 2022Article
- Hematogenous dissemination of pathogenic and non-pathogenicFrontiers in cellular and infection microbiology · 2022Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Leptospira interrogans differs from other spirochetes in that it contains homologs of all the Escherichia coli lpx genes required for the biosynthesis of the lipid A anchor of lipopolysaccharide (LPS). LPS from L. interrogans cells is unusual in that it activates TLR2 rather than TLR4. The structure of L. interrogans lipid A has now been determined by a combination of matrix-assisted laser desorption ionization time-of-flight mass spectrometry, NMR spectroscopy, and biochemical studies. Lipid A was released from LPS of L. interrogans serovar Pomona by 100 degrees C hydrolysis at pH 4.5 in the presence of SDS. Following purification by anion exchange and thin layer chromatography, the major component was shown to have a molecular weight of 1727. Mild hydrolysis with dilute NaOH reduced this to 1338, consistent with the presence of four N-linked and two O-linked acyl chains. The lipid A molecules of both the virulent and nonvirulent forms of L. interrogans serovar Icterohaemorrhagiae (strain Verdun) were identical to those of L. interrogans Pomona by the above criteria. Given the selectivity of L. interrogans LpxA for 3-hydroxylaurate, we propose that L. interrogans lipid A is acylated with R-3-hydroxylaurate at positions 3 and 3' and with R-3-hydroxypalmitate at positions 2 and 2'. The hydroxyacyl chain composition was validated by gas chromatography and mass spectrometry of fatty acid methyl esters. Intact hexa-acylated lipid A of L. interrogans Pomona was also analyzed by NMR, confirming the presence a beta-1',6-linked disaccharide of 2,3-diamino-2,3-dideoxy-d-glucopyranose units. Two secondary unsaturated acyl chains are attached to the distal residue. The 1-position of the disaccharide is derivatized with an axial phosphate moiety, but the 4'-OH is unsubstituted. (1)H and (31)P NMR analyses revealed that the 1-phosphate group is methylated. Purified L. interrogans lipid A is inactive against human THP-1 cells but does stimulate tumor necrosis factor production by mouse RAW264.7 cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.