A novel lipoarabinomannan from the equine pathogen Rhodococcus equi. Structure and effect on macrophage cytokine production.
Abstract: Rhodococcus equi is a major cause of foal morbidity and mortality. We have investigated the presence of lipoglycan in this organism as closely related bacteria, notably Mycobacterium tuberculosis, produce lipoarabinomannans (LAM) that may play multiple roles as virulence determinants. The lipoglycan was structurally characterized by gas chromatography-mass spectrometry following permethylation, capillary electrophoresis after chemical degradation, and (1)H and (31)P and two-dimensional heteronuclear nuclear magnetic resonance studies. Key structural features of the lipoglycan are a linear alpha-1,6-mannan with side chains containing one 2-linked alpha-d-Manp residue. This polysaccharidic backbone is linked to a phosphatidylinositol mannosyl anchor. In contrast to mycobacterial LAM, there are no extensive arabinan domains but single terminal alpha-d-Araf residue capping the 2-linked alpha-d-Manp. The lipoglycan binds concanavalin A and mannose-binding protein consistent with the presence of t-alpha-d-Manp residues. We studied the ability of the lipoglycans to induce cytokines from equine macrophages, in comparison to whole cells of R. equi. These data revealed patterns of cytokine mRNA induction that suggest that the lipoglycan is involved in much of the early macrophage cytokine response to R. equi infection. These studies identify a novel LAM variant that may contribute to the pathogenesis of disease caused by R. equi.
Publication Date: 2002-06-18 PubMed ID: 12072437DOI: 10.1074/jbc.M203008200Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research article investigates a newly discovered lipoarabinomannan present in Rhodococcus equi, an equine pathogen, and its impact on macrophage cytokine production. Structural characteristics of the lipoglycan were studied, and a potential role in the initial macrophage response to R. equi infection was identified.
Characterization of Lipoglycan
- The researchers focused on the structure of the lipoglycan present in Rhodococcus equi. Methods used to analyze the structure included gas chromatography-mass spectrometry following permethylation, capillary electrophoresis after chemical degradation, and specific nuclear magnetic resonance studies.
- Through these analyses, it was found that the lipoglycan has a linear alpha-1,6-mannan structure with side chains containing one 2-linked alpha-d-Manp residue. The backbone of this lipoglycan is linked to a phosphatidylinositol mannosyl anchor.
Comparison with Mycobacterial LAM
- The lipoglycan does not have extensive arabinan domains, unlike mycobacterial lipoarabinomannans. Instead, it contains single terminal alpha-d-Araf residues and is capable of binding concanavalin A and mannose-binding protein, indicative of the presence of t-alpha-d-Manp residues.
Impact on Equine Macrophage Cytokine Production
- The researchers looked at the lipoglycan’s ability to induce cytokines from equine macrophages, comparing this to the reaction of whole cells of R. equi.
- The patterns in cytokine mRNA induction suggest that the lipoglycan plays a significant role in the early macrophage cytokine response to R. equi infection.
Conclusion
- The article concludes by stating that the research has identified a new variant of lipoarabinomannan that likely plays a role in disease pathogenesis caused by R. equi. This innovative finding is critical for future studies aiming to improve the understanding and treatment of diseases instigated by this type of pathogen.
Cite This Article
APA
Garton NJ, Gilleron M, Brando T, Dan HH, Giguère S, Puzo G, Prescott JF, Sutcliffe IC.
(2002).
A novel lipoarabinomannan from the equine pathogen Rhodococcus equi. Structure and effect on macrophage cytokine production.
J Biol Chem, 277(35), 31722-31733.
https://doi.org/10.1074/jbc.M203008200 Publication
Researcher Affiliations
- Institute of Pharmacy, Chemistry and Biomedical Sciences, the University of Sunderland, Sunderland SR2 3SD, United Kingdom.
MeSH Terms
- Animals
- Antigens, Bacterial / chemistry
- Antigens, Bacterial / isolation & purification
- Antigens, Bacterial / pharmacology
- Base Sequence
- Carbohydrate Sequence
- Cytokines / immunology
- DNA Primers
- Fatty Acids / analysis
- Glycerolphosphate Dehydrogenase / genetics
- Horses
- Lipopolysaccharides / chemistry
- Lipopolysaccharides / isolation & purification
- Lipopolysaccharides / pharmacology
- Macrophages / drug effects
- Macrophages / immunology
- Methylation
- Molecular Sequence Data
- Monosaccharides / analysis
- Oligosaccharides / chemistry
- Rhodococcus equi / chemistry
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Grant Funding
- N01-AI-25147 / NIAID NIH HHS
Citations
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