Temperature-dependent phenotypic variation of Campylobacter jejuni lipooligosaccharides

BACKGROUND: Campylobacter jejuni is a major bacterial cause of food-borne enteritis, and its lipooligosaccharide (LOS) plays an initiating role in the development of the autoimmune neuropathy, Guillain-Barré syndrome, by induction of anti-neural cross-reactive antibodies through ganglioside molecular mimicry. RESULTS: Herein we describe the existence and heterogeneity of multiple LOS forms in C. jejuni strains of human and chicken origin grown at 37°C and 42°C, respectively, as determined on sodium dodecyl sulphate-polyacrylamide electrophoresis gels with carbohydrate-specific silver staining and blotting with anti-ganglioside ligands, and confirmed by nuclear magnetic resonance (NMR) spectroscopy. The C. jejuni NCTC 11168 original isolate (11168-O) was compared to its genome-sequenced variant (11168-GS), and both were found to have a lower-M(r )LOS form, which was different in size and structure to the previously characterized higher-M(r )form bearing GM(1 )mimicry. The lower-M(r )form production was found to be dependent on the growth temperature as the production of this form increased from ~5%, observed at 37°C to ~35% at 42°C. The structure of the lower-M(r )form contained a β-D-Gal-(1→3)-β-D-GalNAc disaccharide moiety which is consistent with the termini of the GM(1), asialo-GM(1), GD(1), GT(1 )and GQ(1 )gangliosides, however, it did not display GM(1 )mimicry as assessed in blotting studies but was shown in NMR to resemble asialo-GM(1). The production of multiple LOS forms and lack of GM(1 )mimicry was not a result of phase variation in the genes tested of NCTC 11168 and was also observed in most of the human and chicken isolates of C. jejuni tested. CONCLUSION: The presence of differing amounts of LOS forms at 37 and 42°C, and the variety of forms observed in different strains, indicate that LOS form variation may play a role in an adaptive mechanism or a stress response of the bacterium during the colonization of different hosts.