Lipooligosaccharide allele genotyping enables the prediction of ganglioside mimicking structures on Campylobacter jejuni

Background: The Campylobacter jejuni lipooligosaccharide (LOS) locus genotypes A and B are associated with the development of Guillain-Barré syndrome (GBS). However, high prevalence of these genotypes in strains isolated from patients with uncomplicated enteritis suggests that additional bacterial factors could contribute to the onset of GBS.

Objective: To assess whether allele variations within the C. jejuni LOS locus of A and B genotypes can differentiate GBS- from uncomplicated enteritis-associated strains, or determine the structure of the ganglioside mimic produced.

Methods: PCR and sequencing were performed to assess the prevalence of LOS alleles A1/2 and B1/2 in a large collection of GBS- and enteritis-associated strains. Mass spectrometry was used to determine the LOS structures produced by the strains.

Results: The A1 and B2 alleles were most prevalent (each ~80%) among LOS class A and B strains isolated from GBS as well as enteritis patients. Sialylation of the inner galactose of the outer core LOS was only observed for strains with an A1 or B1 allele. C. jejuni with the A1 allele predominantly (88%) synthesized GM1a and GD1a ganglioside mimics. In strains with the A2 and B2 allele, GM1b and/or GD1c-mimics were frequently (86%) observed. Point mutations within LOS biosynthesis genes explained alternate LOS structures in specific strains.

Conclusions: Allele variations within the LOS locus A and B genotypes do not distinguish GBS- from uncomplicated enteritis-associated strains. However, LOS allele genotyping is a powerful tool that can be used to predict which ganglioside mimicking structures are synthesized by C. jejuni strains.