A Haemophilus influenzae strain associated with Fisher syndrome expresses a novel disialylated ganglioside mimic.
The non-typeable Haemophilus influenzae strain DH1 was isolated from a 25 year old male patient with Fisher syndrome, a postinfectious autoimmune condition characterized by the presence of anti-GQ1b IgG antibodies that target and initiate damage to peripheral nerves. DH1 was found to display an alphaNeuAc(2-8)alphaNeuAc(2-3)betaGal branch bound to the tetraheptosyl backbone core of its lipooligosaccharide (LOS). The novel sialylation pattern was found to be dependent on the activity of a bifunctional sialyltransferase, Lic3B, which catalyzes the addition of both the terminal and subterminal sialic acid residues. Patient serum IgGs bind to DH1 LOS, and the reactivity is significantly influenced by the presence of sialylated glycoforms. The display by DH1, of a surface glycan that mimics the terminal trisaccharide portion of disialosyl-containing gangliosides, provides strong evidence for its involvement in the development of Fisher syndrome.
Houliston
R Scott
RS
Institute for Biological Sciences, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Koga
Michiaki
M
Li
Jianjun
J
Jarrell
Harold C
HC
Richards
James C
JC
Vitiazeva
Varvara
V
Schweda
Elke K H
EK
Yuki
Nobuhiro
N
Gilbert
Michel
M
D000328:Adult; D002240:Carbohydrate Sequence; D005732:Gangliosides / Q000378:metabolism*; D006193:Haemophilus influenzae / Q000502:physiology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D019846:Miller Fisher Syndrome / Q000382:microbiology*; D018716:Molecular Mimicry; D008969:Molecular Sequence Data
D005732:Gangliosides