Antigenic similarities in lipopolysaccharides of Haemophilus and Neisseria and expression of a digalactoside structure also present on human cells

Mouse monoclonal antibodies (MAbs) DP8 [immunoglobulin G1()] and DH24 [immunoglobulin M()], which are specific for Haemophilus ducreyi lipopolysaccharide (LPS), were generated by fusing mouse myeloma NS0 cells with spleen cells of BALB/c mice immunized with a total membrane preparation of H. ducreyi. MAb DP8 reacted in whole-cell enzyme immunoassay (EIA) and colony dot immunoblotting with all 50 strains of H. ducreyi but not with any other bacteria tested, which suggests an exposed and species-specific epitope on the H. ducreyi cell surface. This conclusion was supported by the finding that DP8 bound to all six H. ducreyi LPSs tested but not to any of the Haemophilus influenzae or enterobacterial LPSs or synthetic glycoconjugates. The MAb DH24 bound to 43 of 50 strains of H. ducreyi and to few strains of H. influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis, as evaluated by whole-cell EIA and colony dot immunoblotting. The MAb DH24 reacted with five of the six H. ducreyi LPSs tested and with the lacto-N-neotetraose (Gal␤134GlcNAc␤133Gal␤13 4Glc) series of synthetic glycoconjugates, as determined by EIA. By using polysaccharides obtained after both mild acidic hydrolysis and strong alkali treatment and dephosphorylated samples as inhibitors of the MAbs binding to H. ducreyi LPS antigens, it could be shown that phosphate groups were essential for the binding of DP8 to LPS but that they did not affect antigenic recognition by DH24. None of the MAbs bound to isolated lipid A, but aggregation caused by the fatty acids of lipid A was essential for epitope recognition.

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“…Through this molecular mimicry, the bacteria can avoid the host defense mechanisms as has previously been reported (17,21,35).…”

Section: Discussionmentioning

confidence: 84%

Monoclonal antibodies againstHaemophilus ducreyi lipooligosaccharide and their diagnostic usefulness

Ahmed

Borrelli

Jonasson

et al. 1995

Eur. J. Clin. Microbiol. Infect. Dis.

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“…In the present study, we did not find a useful correlation between our strains and binding of this antibody. However, mAb 4C4, previously reported to bind a digalactoside of H. influenzae LPS (Virji et al, 1990), did show strain-dependent phase-variable expression of LPS epitopes dependent upon lex2 activity. The generation of more than one mAb 4C4-reactive phenotype for strain RM7004 noted in this study and reported by Roche et al (1994) until now has not been understood.…”

Section: Discussionmentioning

confidence: 93%

“…This is contrary to the variable reactivity in colony phenotype demonstrated by other strains when reacted with mAb 5G8, in previous studies (Jarosik & Hansen, 1994). Differences in the pattern of reactivity between strains were observed with mAb 4C4; this antibody binds a digalactoside moiety on H. influenzae LPS (Virji et al, 1990). The majority of colonies of wild-type strain RM7004 (>98 %) reacted (R) with mAb 4C4 and a negative (off; O) phenotype was represented at a level of less than 1 % (Fig.…”

Section: Transcription and Translation Of Lex2a And Lex2bmentioning

confidence: 99%

The role of lex2 in lipopolysaccharide biosynthesis in Haemophilus influenzae strains RM7004 and RM153

et al. 2003

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The locus lex2, comprising lex2A and lex2B, contributes to the phase-variable expression of lipopolysaccharide (LPS) of Haemophilus influenzae and was found to be present in 74 % of strains investigated. lex2A contains 59-GCAA repeats which vary in number from 4 to 46 copies between strains. The locus was cloned from the serotype b strains RM7004 and RM153 and showed >99 % nucleotide sequence identity between these strains and the published lex2 sequence. Disruption of the lex2B gene in strain RM7004 resulted in truncation of some LPS glycoforms, shown by gel fractionation, with only one glycoform reacting with a digalactosidespecific monoclonal antibody, 4C4, compared with four LPS glycoforms in the more elongated LPS of the parent strain. Mass spectrometry and NMR analyses of LPS from the lex2B mutant revealed loss of the terminal digalactoside as well as the second b-glucose extending from the first heptose of the inner core. The authors conclude that Lex2B is the b-(1-4)-glucosyltransferase that adds the second b-glucose to the first b-glucose as part of the oligosaccharide extension from the first heptose of the LPS of strain RM7004. Investigation of the expression of the lex2 locus indicated that the genes are co-transcribed and that both reading frames are required for addition of this second b-glucose in a phase-variable manner.

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“…This form of molecular mimicry exhibited by M. catarrhalis may provide the pathogen with an advantage for evading host defence mechanisms. This structural feature also occurs in LPS of pathogenic strains of Haemophilus injluenzae (24,25) and Neisseria spp. (25) and it has been implicated in virulence potential (26).…”

Section: +6)-p-d-glcpn-(l+6)-d-glcnol Unit Derived From the Lipid A Rmentioning

confidence: 99%

Structural elucidation of the backbone oligosaccharide from the lipopolysaccharide of Moraxella catarrhalis serotype A

Masoud¹,

Perry²,

Brisson³

et al. 1994

Can. J. Chem.

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. Can. J. Chem. 72, 1466Chem. 72, (1994.The cell-surface lipopolysaccharide produced by Mornxella catarrhalis serotype A is composed of a hydrophobic lipid A moiety and an oligosaccharide, but lacks high-molecular-weight 0-polysaccharide chains. The oligosaccharide component is composed of D-glucose, D-galactose, D-glucosamine, and 3-deoxy-D-manno-octulosonic acid. The carbohydrate backbone was obtained from the lipopolysaccharide by employing a reaction sequence involving deacylation, dephosphorylation, and reduction of the reducing D-glucosamine terminus of the lipid A moiety. Structural analysis of the backbone oligosaccharide employed a combination of microanalytical methods and nuclear magnetic resonance spectroscopy. Homo-and hetero-nuclear chemical shift correlation techniques and nuclear Overhauser enhancement (NOE) experiments led to the unambiguous assignment of the [Traduit par la Redaction]

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Antigenic similarities in lipopolysaccharides of Haemophilus and Neisseria and expression of a digalactoside structure also present on human cells

Cited by 93 publications

References 18 publications

Monoclonal antibodies againstHaemophilus ducreyi lipooligosaccharide and their diagnostic usefulness

Monoclonal antibodies againstHaemophilus ducreyi lipooligosaccharide and their diagnostic usefulness

The role of lex2 in lipopolysaccharide biosynthesis in Haemophilus influenzae strains RM7004 and RM153

Structural elucidation of the backbone oligosaccharide from the lipopolysaccharide of Moraxella catarrhalis serotype A

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