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J. Biol. Chem., Vol. 277, Issue 35, 31722-31733, August 30, 2002
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From the 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 1H and 31P and
two-dimensional heteronuclear nuclear magnetic resonance studies. Key
structural features of the lipoglycan are a linear
A Novel Lipoarabinomannan from the Equine Pathogen
Rhodococcus equi
STRUCTURE AND EFFECT ON MACROPHAGE CYTOKINE PRODUCTION*
§,
,, and
Institute of Pharmacy, Chemistry and
Biomedical Sciences, the University of Sunderland,
Sunderland SR2 3SD, United Kingdom, ¶ Institut de
Pharmacologie et de Biologie Structurale du CNRS, 205 Route de
Narbonne, 31077 Toulouse Cedex 4, France, the Department of
Pathobiology, University of Guelph, Guelph, Ontario N1G 2W1, Canada,
and ** College of Veterinary Medicine, University of Florida,
Gainesville, Florida 32610-0136
-1,6-mannan with
side chains containing one 2-linked -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
-D-Araf residue capping the 2-linked
-D-Manp. The lipoglycan binds concanavalin A
and mannose-binding protein consistent with the presence of t--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.
*
This work was supported by The Horserace Betting Levy Board
Grant vet/prj/652, by the Natural Sciences and Engineering Research Council of Canada, and by European Community Program TB Vaccine Cluster
Contract QLK2-CT-1999-01093.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 44 191 515 2995; Fax: 44 191 515 3747; E-mail:
iain.sutcliffe@sunderland.ac.uk.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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