|Godschalk, Peggy C.r.|
Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 10/10/2004
Publication Date: 6/1/2005
Citation: Gilbert, M., Godschalk, P., Parker, C., Endtz, H., Wakarchuk, W.W. 2005. Genetic basis for the variation in the lipooligosaccharide outer core of campylobacter jejuni and possible association of glycosyltransferase genes with post-infectious neuropathies. In: Ketley, J., Konkel, M.E., editors. Campylobacter jejuni: New Perspectives in Molecular and Cellular Biology. Norfolk, UK, Horizon Scientific Press, 219-248. Interpretive Summary: The lipooligosaccharide (LOS) of Campylobacter jejuni is an important outer surface component and a virulence factor. In some C. jejuni strains it mimics the gangliosides present in mammalian cells and tissues. The LOS varies within a strain by frameshifts in genes due to polynucleotide repeats and slipped strand mispairing. The glycosyltransferases encoded by these genes are synthesized in some cells and not others and this is reflected in full or truncated LOS. This genetic mechanism of variation of LOS outer cores in C. jejuni provides a good example of adaptive evolution strategies used by mucosal pathogens to modulate the structure of a cell-surface carbohydrate in order to better survive in a host. The biological effects of different LOS structures are not well understood, but it is probable that they are involved in different mechanisms depending upon the host tissue and other environmental factors. An intriguing aspect of the significant molecular and antigenic mimicry in C. jejuni LOS is that similar mimicry is observed in other human pathogens and commensals that exist in respiratory niches; they do not resemble the lipopolysaccharide (LPS) of most enteric bacteria.
Technical Abstract: The lipooligosaccharide (LOS) of Campylobacter jejuni displays considerable variation in the structure of its outer core. Micro-array and PCR probing studies have shown that there is extensive variation in the gene content of the locus responsible for the biosynthesis of the LOS. DNA sequencing of this locus from multiple strains has demonstrated four other mechanisms that C. jejuni uses to vary its LOS outer core: a) phase variation because of homopolymeric tracts, b) gene inactivation by the deletion or insertion of a single base (without phase variation), c) single mutation leading to the inactivation of a glycosyltransferase and d) single or multiple mutations leading to glycosyltransferases with different acceptor specificities. These four mechanisms have resulted in “allelic” glycosyltransferases with potential to phase-vary their expression or modulate their specificity. Alleles representing each of these four mechanisms have been found for some of the outer core glycosyltransferases. Although the various types of alleles have presumably appeared through vertical evolution there is also evidence that horizontal exchange has further contributed to LOS outer core variation. The genetic bases for the variation of LOS outer cores in C. jejuni provide a good example of various adaptive evolution strategies used by a mucosal pathogen to modulate the structure of a cell-surface carbohydrate in order to better survive in a host. We also discuss the association of specific LOS biosynthesis genes with C. jejuni stains isolated from patients who developed Guillain-Barré and Miller-Fisher syndromes. 06/04/03