Phase variation of Campylobacter jejuni 81-176 lipooligosaccharide affects ganglioside mimicry and invasiveness in vitro.
The outer cores of the lipooligosaccharides (LOS) of many strains of Campylobacter jejuni mimic human gangliosides in structure. A population of cells of C. jejuni strain 81-176 produced a mixture of LOS cores which consisted primarily of structures mimicking GM(2) and GM(3) gangliosides, with minor amounts of structures mimicking GD(1b) and GD(2). Genetic analyses of genes involved in the biosynthesis of the outer core of C. jejuni 81-176 revealed the presence of a homopolymeric tract of G residues within a gene encoding CgtA, an N-acetylgalactosaminyltransferase. Variation in the number of G residues within cgtA affected the length of the open reading frame, and these changes in cgtA corresponded to a change in LOS structure from GM(2) to GM(3) ganglioside mimicry. Site-specific mutation of cgtA in 81-176 resulted in a major LOS core structure that lacked GalNAc and resembled GM(3) ganglioside. Compared to wild-type 81-176, the cgtA mutant showed a significant increase in invasion of INT407 cells. In comparison, a site-specific mutation of the neuC1 gene resulted in the loss of sialic acid in the LOS core and reduced resistance to normal human serum but had no affect on invasion of INT407 cells.
Guerry
Patricia
P
Enteric Diseases Program, Naval Medical Research Center, Silver Spring, Maryland 20910, USA. guerryp@nmrc.navy.mil
Szymanski
Christine M
CM
Prendergast
Martina M
MM
Hickey
Thomas E
TE
Ewing
Cheryl P
CP
Pattarini
Dawn L
DL
Moran
Anthony P
AP
D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics*; D001426:Bacterial Proteins; D001483:Base Sequence; D016123:Campylobacter jejuni / Q000235:genetics*; D002240:Carbohydrate Sequence; D003001:Cloning, Molecular; D004269:DNA, Bacterial; D005678:G(M2) Ganglioside / Q000737:chemistry; D005679:G(M3) Ganglioside / Q000737:chemistry; D005732:Gangliosides / Q000737:chemistry*; D015870:Gene Expression; D005798:Genes, Bacterial; D014644:Genetic Variation; D008070:Lipopolysaccharides / Q000032:analysis; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics; D016296:Mutagenesis; D017422:Sequence Analysis, DNA; D016339:Spectrometry, Mass, Fast Atom Bombardment / Q000379:methods
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D005679:G(M3) Ganglioside; D005732:Gangliosides; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; C033851:ganglioside, GD1b; D005678:G(M2) Ganglioside; C019403:ganglioside, GD2; C108621:CgtA protein, bacteria; D020559:Monomeric GTP-Binding Proteins