Relapsing fever Borrelia binds to neolacto glycans and mediates rosetting of human erythrocytes
- Betty P. Guoa,
- Susann Tenebergb,
- Robert Müncha,
- Daiyo Terunumac,
- Ken Hatanoc,
- Koji Matsuokac,
- Jonas Ångströmb,
- Thomas Borénd and
- Sven Bergströma,1
- aUniversity of Umeå, Department of Molecular Biology, Umeå, Sweden;
- bUniversity of Gothenburg, Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, Göteborg, Sweden;
- cSaitama University, Faculty of Engineering, Department of Functional Materials Science, Saitama, Japan; and
- dUniversity of Umeå, Department of Biophysics and Medical Biochemistry, Umeå, Sweden
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Edited by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved September 23, 2009 (received for review June 2, 2009)
Abstract
A hallmark of acute relapsing fever borreliosis is severe bacteremia. Some Borrelia species, such as B. duttonii and B. crocidurae, associate with erythrocytes and induce aggregation recognized as erythrocyte rosetting. Erythrocyte rosettes contribute to disease severity by increased tissue invasiveness (such as invasion of CNS and encephalitis), hemorrhaging, and reduced blood flow in affected microcapillaries. Here we report that relapsing fever Borrelia binds to neolacto (Galβ4GlcNAcβ3Galβ4Glcβ1)–carrying glycoconjugates that are present on human erythrocytes. This interaction is of low affinity but is compensated for by the multivalency of neo-lacto-oligosaccharides on the erythrocyte cell surface. Hence, the protein–carbohydrate interaction is dependent on multivalent neolacto-glycans to mediate binding.
Footnotes
- 1To whom correspondence should be addressed. E-mail: sven.bergstrom{at}molbiol.umu.se
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Author contributions: B.P.G., S.T., T.B., and S.B. designed research; B.P.G., S.T., R.M., and J.A. performed research; S.T., D.T., K.H., K.M., and J.A. contributed new reagents/analytic tools; B.P.G., S.T., T.B., and S.B. analyzed data; and B.P.G., S.T., and T.B. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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↵* The glycosphingolipid nomenclature follows the recommendations of the IUPAC-IUB Commission on Biochemical Nomenclature (28). It is assumed that NeuAc, NeuGc, Gal, Glc, GlcNAc, and GalNAc are of the D-configuration, Fuc of the L-configuration, and all sugars are present in the pyranose form.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0905470106/DCSupplemental.
