Autor(es): Linton, D.; Gilbert, M.; Hitchen, P. G.; Dell, A.; Morris, H. R.; Wakarchuk, W. W.; Gregson, N. A.; Wren, B. W.

Resumo: Ganglioside mimicry by Campylobacter jejuni lipo-oligosaccharide (LOS) is thought to be a critical factor in the triggering of the Guillain-Barre and Miller-Fisher syndrome neuropathies after C. jejuni infection. The combination of a completed genome sequence and a ganglioside GM sub(1)-like LOS structure makes C. jejuni NCTC 11168 a useful model strain for the identification and characterization of the genes involved in the biosynthesis of ganglioside-mimicking LOS. Genome analysis identified a putative LOS biosynthetic cluster and, from this, we describe a putative gene (ORF Cj1139c), which we have termed wlaN, with a significant level of similarity to a number of bacterial glycosyltransferases. Mutation of this gene in C. jejuni NCTC 11168 resulted in a LOS molecule of increased electrophoretic mobility, which also failed to bind cholera toxin. Comparison of LOS structural data from wild type and the mutant strain indicated lack of a terminal beta -1,3-linked galactose residue in the latter. The wlaN gene product was demonstrated unambiguously as a beta -1,3 galactosyltransferase responsible for converting GM sub(2)-like LOS structures to GM sub(1)-like by in vitro expression. We also show that the presence of an intragenic homopolymeric tract renders the expression of a functional wlaN gene product phase variable, resulting in distinct C. jejuni NCTC 11168 cell populations with alternate GM sub(1) or GM sub(2) ganglioside-mimicking LOS structures. The distribution of wlaN among a number of C. jejuni strains with known LOS structure was determined and, for C. jejuni NCTC 12500, similar wlaN gene phase variation was shown to occur, so that this strain has the potential to synthesize a GM sub(1)-like LOS structure as well as the ganglioside GM sub(2)-like LOS structure proposed in the literature.

Palavras-Chave: lipooligosaccharides; ganglioside GM1; Aquatic organisms; Biosynthesis; Nervous system; Human diseases; Genes; Pathogenic bacteria; Microorganisms; Enzymes; Aetiology; Phase variations; Guillain-Barre syndrome; Ganglioside galactosyltransferase; Campylobacter jejuni; Freshwater

Imprenta: Molecular Microbiology, v. 37, n. 3, p. 501-514, 2000

Descritores: Guillain-Barre Syndrome and Cell ; Guillain-Barre Syndrome and Genome ; Guillain-Barre Syndrome and Molecular Structure ; Guillain-Barre Syndrome and Infectious diseases

Data de publicação: 2000

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