Molecular mimicry in Campylobacter jejuni: role of the lipo-oligosaccharide core oligosaccharide in inducing anti-ganglioside antibodies

Authors


  • Editor: Alex van Belkum

Correspondence: Benjamin N. Fry, Department of Biotechnology and Environmental Biology, RMIT University, Bundoora, Vic. 3083, Australia.
Tel.: +61 3 99257125; fax: +61 3 99257110; e-mail: ben.fry@rmit.edu.au

Abstract

Campylobacter jejuni is recognized as the most common identifiable pathogen associated with the development of Guillain–Barré syndrome (GBS), an acute autoimmune-mediated disease affecting the peripheral nervous system. The immune response to ganglioside-like structures in lipo-oligosaccharides (LOSs) of certain C. jejuni strains is thought to cross-react with human nerve gangliosides and induce GBS. To study the involvement of LOSs in the pathogenesis of Campylobacter-induced GBS, we created truncated LOS molecules by inactivating the waaF gene in a GBS-associated isolate of C. jejuni. Gas Chromatography–MS analysis of the waaF mutant LOSs revealed a marked reduction in sugar content, including sialic acid and galactose. GM1 and GD1a-like mimicry was not detected in the waaF mutant by Western blot analysis with cholera toxin B and anti-GD1a antibodies. Mice immunized with the waaF mutant failed to develop anti-GM1 or anti-GD1a antibodies. The waaF mutant also showed reduced adherence to and invasion of INT-407 cells. The results indicate that the LOS of C. jejuni HB93-13 is essential for adherence and invasion as well as for anti-ganglioside antibody induction.

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