A<i>Haemophilus influenzae</i>Strain Associated with Fisher Syndrome Expresses a Novel Disialylated Ganglioside Mimic

Houliston, R. Scott; Koga, Michiaki; Li, Jianjun; Jarrell, Harold C.; Richards, James C.; Vitiazeva, Varvara; Schweda, Elke K. H.; Yuki, Nobuhiro; Gilbert, Michel

doi:10.1021/bi700685s

Cited by 45 publications

(29 citation statements)

References 44 publications

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“…HepIV-containing LPS glycoforms have previously been shown to include epitopes that influence serum resistance of NTHi strains (Erwin et al, 2006b;Houliston et al, 2007). For our strains, the killing effect of normal human serum was somewhat enhanced for each of the losA1, losB1, losA2 and losB2 mutants of both strain 176 (Fig.…”

Section: Effect Of Mutation Of Losa and Losb Genesmentioning

confidence: 70%

“…1a). This HepIV residue can be substituted by further hexose extensions (Houliston et al, 2007;Månsson et al, 2003b), can be branched (Månsson et al, 2003a) or can be substituted by phosphocholine (PCho) (Fox et al, 2008). The gene repertoire required for the synthesis of the H. influenzae LPS molecule has been identified in a number of key strains (Hood et al, 1996a(Hood et al, , 2001 following analyses based upon the whole-genome sequence of strain Rd (Fleischmann et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Genes required for the synthesis of heptose-containing oligosaccharide outer core extensions in Haemophilus influenzae lipopolysaccharide

et al. 2010

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Heptose-containing oligosaccharides (OSs) are found in the outer core of the lipopolysaccharide (LPS) of a subset of non-typable Haemophilus influenzae (NTHi) strains. Candidate genes for the addition of either L-glycero-D-manno-heptose (LD-Hep) or D-glycero-D-manno-heptose (DD-Hep) and subsequent hexose sugars to these OSs have been identified from the recently completed genome sequences available for NTHi strains. losA1/losB1 and losA2/losB2 are two sets of related genes in which losA has homology to genes encoding glycosyltransferases and losB to genes encoding heptosyltransferases. Each set of genes is variably present across NTHi strains and is located in a region of the genome with an alternative gene organization between strains that contributes to LPS heterogeneity. Dependent upon the strain background, the LPS phenotype, structure and serum resistance of strains mutated in these genes were altered when compared with the relevant parent strain. Our studies confirm that losB1 and losB2 usually encode DDheptosyl-and LD-heptosyl transferases, respectively, and that losA1 and losA2 encode glycosyltransferases that play a role in OS extensions of NTHi LPS.

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Section: Effect Of Mutation Of Losa and Losb Genesmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Genes required for the synthesis of heptose-containing oligosaccharide outer core extensions in Haemophilus influenzae lipopolysaccharide

et al. 2010

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“…Other microorganisms that trigger GBS, including Haemophilus infl uenza and Mycoplasma pneumonia, also bear ganglioside and glycolipid mimics, indicating that this mechanism might be a more general mechanism of the immunological induction pathway for GBS, rather than being restricted to Campylobacter infection. In this regard, analysis of a strain of Haemophilus infl uenza from a patient with MFS also revealed a homologous bifunctional sialyltransferase (Lic3B) producing a disialoysl group linked to the terminal galactose of the LOS (Houliston et al 2007 ). One mechanism by which cross reactivity can occur between gangliosides which share such groups, such as bacterial GD1c and host GQ1b has been demonstrated by epitope mapping using saturation transfer difference NMR spectroscopy.…”

Section: The Origin and Nature Of Anti-ganglioside Antibodiesmentioning

confidence: 98%

Glycoconjugates and Neuroimmunological Diseases

Willison

2014

Advances in Neurobiology

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A wide range of neuroimmunological diseases affect the central and peripheral nervous systems. These disorders are caused by autoimmune attack directed against structurally and functionally diverse nervous system antigens. One such category comprises peripheral nervous system (PNS) diseases, termed peripheral neuropathies, in which the target antigens for autoantibody-directed nerve injury are glycan structures borne by glycoproteins and glycolipids, particularly gangliosides that are concentrated in peripheral nerve. The archetypal PNS disorder is the acute paralytic disease, Guillain-Barré syndrome (GBS) in which autoantibodies against glycolipids arise in the context of acute infections that precede the clinical onset, notably Campylobacter jejuni enteritis. In addition, several chronic autoimmune neuropathies are associated with IgM antibodies directed against nerve glycans including sulphated glucuronic acid epitopes present on myelin-associated glycoprotein and sulphated glucuronyl paragloboside, a range of disialylated gangliosides including GD1b and GD3, and GM1 ganglioside. This chapter describes the immunological, pathological and clinical features of these disorders in the context of our broader knowledge of the glycobiology underpinning this neuroimmunological field.

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“…Campylobacter jejuni [22] and Haemophilus influenzae [23] have been reported as infectious agents prior to the onset of Fisher syndrome, and the molecular mimicry between the structures of the lipooligosaccharides of these bacteria and GQ1b has also been noted [24,25]. Protein levels in the cerebrospinal fluid, without pleocytosis, are usually elevated in patients with Fisher syndrome.…”

Section: Laboratory Findingsmentioning

confidence: 99%

Fisher Syndrome

Mori

Kuwabara

2010

Curr Treat Options Neurol

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Fisher syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia. It is considered a variant form of Guillain-Barré syndrome, which is associated with anti-GQ1b antibodies. During initial examinations of patients, physicians must rule out other neurologic disorders or conditions that resemble Fisher syndrome, such as vitamin B1 deficiency (Wernicke's encephalopathy), vascular disease, multiple sclerosis, collagen disease, Behçet disease, sarcoidosis, neoplasm of the brainstem, and infectious diseases such as diphtheria, botulism, and viral infections (eg, herpes encephalitis). The acute phase of Fisher syndrome should be carefully observed to see if it occurs concomitantly with Guillain-Barré syndrome or if there is development to Bickerstaff brainstem encephalitis, as these require specific immune treatments. Typically, Fisher syndrome has a fairly good natural course. Although several reports have suggested the possible efficacy of immunotherapies such as plasmapheresis and intravenous immunoglobulins (IVIg) in treating Fisher syndrome, there have been no randomized controlled studies. Large retrospective studies have suggested that neither plasmapheresis nor IVIg alters the clinical outcome of patients with Fisher syndrome, probably because of the good spontaneous recovery in these patients. Therefore, Fisher syndrome alone does not necessarily require immunotherapy. To accelerate the start of recovery, IVIg can be given, but it is important to first obtain informed consent from patients after the potential risks of blood products are explained. When overlap with Guillain-Barré syndrome or development to Bickerstaff brainstem encephalitis occurs, plasma exchange or IVIg should be administered as early as possible because Guillain-Barré syndrome can cause respiratory failure or severe weakness with axonal degeneration, and Bickerstaff brainstem encephalitis may not have as good a natural course as Fisher syndrome alone. There have been no prospective, controlled studies (randomized or nonrandomized) of the use of immunotherapy to treat Fisher syndrome. To evaluate the efficacy of immunotherapies used to treat Fisher syndrome, large prospective studies are required.

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AHaemophilus influenzaeStrain Associated with Fisher Syndrome Expresses a Novel Disialylated Ganglioside Mimic

Cited by 45 publications

References 44 publications

Genes required for the synthesis of heptose-containing oligosaccharide outer core extensions in Haemophilus influenzae lipopolysaccharide

Genes required for the synthesis of heptose-containing oligosaccharide outer core extensions in Haemophilus influenzae lipopolysaccharide

Glycoconjugates and Neuroimmunological Diseases

Fisher Syndrome

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