An Updated Classification System and Review of the Lipooligosaccharide Biosynthesis Gene Locus in Campylobacter jejuni

Abstract

Lipooligosaccharide (LOS) is an integral component of the Campylobacter cell membrane with a structure of core oligosaccharides forming inner and outer core regions and a lipid A moiety. The gene content of the LOS core biosynthesis cluster exhibits extensive sequence variation, which leads to the production of variable cell surface LOS structures in Campylobacter. Some LOS outer core molecules in Campylobacter jejuni are molecular mimics of host structures (such as neuronal gangliosides) and are thought to trigger neuronal disorders (particularly Guillain-Barré syndrome and Miller Fisher syndrome) in humans. The extensive genetic variation in the LOS biosynthesis gene cluster, a majority of which occurs in the LOS outer core biosynthesis gene content present between lgtF and waaV, has led to the development of a classification system with 23 classes (A-W) and four groups (1-4) for the C. jejuni LOS region. This review presents an updated and simplified classification system for LOS typing alongside an overview of the frequency of C. jejuni LOS biosynthesis genotypes and structures in various C. jejuni populations.

Keywords: Campylobacter jejuni; Guillain–Barré syndrome; Miller Fisher syndrome; ganglioside mimics; lipooligosaccharide.

FIGURE 1

A summary of the different host–pathogen factors that contribute to the complexity of Guillain–Barré syndrome (GBS) development.

FIGURE 2

A representation of C. jejuni 11168 lipooligosaccharide (LOS) core biosynthesis gene cluster and its LOS structure. Each arrow represents an individual LOS core biosynthesis gene, and its direction indicates the direction of gene transcription. A LOS biosynthesis gene in yellow encodes an enzyme to catalyze the addition of a KDO molecule to lipid A. LOS biosynthesis genes in light pink encode enzymes for the synthesis of LOS inner core structure. LOS biosynthesis genes in green encode enzymes for the synthesis of LOS outer core structure, where LOS genes in light green (neuB1, neuC1, and cgtA/neuA1) synthesize sialic acid to incorporate into the outer core. LOS genes in white (gmhA, waaE, waaD, and gmhB) synthesize heptoses for inner core. Glycan structures were drawn according to the Symbol Nomenclature For Glycans (SNFG).

FIGURE 3

Simplified C. jejuni lipooligosaccharide (LOS) locus classification system. LOS classes are classified into the previously established four groups on the basis of sharing similar LOS biosynthesis gene content. Arrows in checked boxes: LOS biosynthesis gene content, shared between the classes within a LOS group; Blue arrows: Variable LOS biosynthesis genes, located between lgtF (orf3) and waaV (orf12); pink arrows: LOS biosynthesis genes, commonly present in all LOS classes. Genes are numbered according to the Parker et al. (2005) numbering system. Arrow direction represents the direction of gene transcription.

FIGURE 4

A comparison of previous findings of distribution of C. jejuni lipooligosaccharide (LOS) locus genotypes in various C. jejuni populations. ENT, C. jejuni isolates from enteritis patients; GBS, C. jejuni isolates from GBS patients; chick, C. jejuni isolates from chicken; BB infection, C. jejuni isolates from patients with blood-borne infections.