Molecular mimicry in Campylobacter jejuni: role of the lipo-oligosaccharide core oligosaccharide in inducing anti-ganglioside antibodies.
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.
Perera
Viraj N
VN
Department of Biotechnology and Environmental Biology, RMIT University, Bundoora, Victoria, Australia.
Nachamkin
Irving
I
Ung
Huong
H
Patterson
John H
JH
McConville
Malcolm J
MJ
Coloe
Peter J
PJ
Fry
Benjamin N
BN
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D002169:Campylobacter Infections / Q000276:immunology* / Q000378:metabolism; D016123:Campylobacter jejuni / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D005732:Gangliosides / Q000276:immunology*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005964:Glucosyltransferases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D007114:Immunization / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000276:immunology* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D037521:Virulence Factors
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D005732:Gangliosides; D009844:Oligosaccharides; D037521:Virulence Factors; D005964:Glucosyltransferases