LIPO-OLIGOSACCHARIDE BIOSYNTHESIS CLUSTER GENE VARIATION IN CAMPYLOBACTER JEJUNI ISOLATED FROM PATIENTS WITH GUILLAIN BARRE SYNDROME

Abstract

Intro: Lipo-oligosaccharide (LOS) is the most important virulence factor of Campylobacter jejuni that structurally mimics human nerve ganglioside and consequently triggers Guillain-Barre´ syndrome (GBS) as a post-infectious sequela of gastroenteritis. We investigated the variations within the genomic content of LOS in C. jejuni isolated from patients with GBS or enteritis to find out their contribution to GBS induction. Methods: Seven GBS-associated C. jejuni strains were isolated and sequenced using Illumina NextSeq platform. We analyzed LOS-region of GBS-associated C. jejuni strains (n=7, Bangladesh; n=10, Peru, USA, Netherlands) with respect to enteritis-associated strains (n=16, Bangladesh, Netherlands & Canada) and reference genome C. jejuni NCTC11168 using bioinformatics pipelines. Findings: The frequency of nucleotide-variation within LOS region of C. jejuni was substantially greater in GBS-associated strains than enteritis-associated strains (p=0.002). However, no unique single-nucleotide polymorphism (SNP), multiple-nucleotide polymorphism (MNP), or complexes of SNPs were detected in GBS-associated genes (cgtA, cgtB, cstII, cstIII, and wlaN). The cst-II gene (n=15) was predominant in GBS-associated strains compared to cst-III gene (n=2). The cst-II(Thr51) gene was frequently present in GBS-associated strains of Bangladesh, USA, and Netherlands with expression of GM1/GD1 epitope (78%), whereas those with cst-II(Asn51) had the GA2 and GD3 epitopes. cst-II(Asn51) was common in Peruvian strains. Peruvian strains isolated from acute motor axonal neuropathy (AMAN) variant were identical and closely related to 2 strains of AMAN variant from Bangladesh. Phase variable (PV) genes were prevalent in LOS-regions of Bangladeshi and Canadian strains. Among the 34 PV genes possessing repeat tracts, most short sequence repeats were identified as poly-G while five were poly-T and one poly-TA. Conclusion: The frequency of cst-II (Thr51) gene and nucleotide-variation were higher within LOS locus of GBS-associated C. jejuni. Our results support that genetic polymorphism of C. jejuni modifies the substrate specificity of LOS biosynthesis enzyme and autoantibody reactivity that determines the clinical presentation of GBS.