Temperature-dependent phenotypic variation of campylobacter jejuni lipooligosaccharides

Abstract

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-Barre 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 degrees C and 42 degrees 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 similar to 5%, observed at 37 degrees C to similar to 35% at 42 degrees C. The structure of the lower-M(r) form contained a beta-D-Gal-(1 -> 3)-beta-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 degrees 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.