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

Abstract

**Background**: The *Campylobacter jejuni* lipooligosaccharide (LOS) locus genotypes A and B are associated with the development of Guillain-Barre 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.