In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation.

Mandrell, Robert E.; Lesse, Alan J.; Sugai, James V.; Shero, Marlene; Griffiss, J. McLeod; Cole, Jeffrey A.; Parsons, Nick; Smith, H.; Morse, S. A.; Apicella, Michael A.

doi:10.1084/jem.171.5.1649

Cited by 171 publications

(141 citation statements)

References 51 publications

Supporting

Mentioning

137

Contrasting

Order By: Relevance

“…Gonococci with sialylated LOS are resistant to C-mediated lysis and less susceptible to C-dependent phagocytosis (45). In meningococci, both the capsule and LOS are important factors for serum resistance (36,46).…”

Section: Discussionmentioning

confidence: 99%

Binding of the Complement Inhibitor C4bp to Serogroup BNeisseria meningitidis

Jarva

Ram

Vogel

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor C4b-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus strain (H44/76) and to 11 isogenic mutants thereof that differed in capsule expression, lipo-oligosaccharide sialylation, and/or expression of either porin (Por) A or PorB3. All strains expressing PorA bound radiolabeled C4bp, whereas the strains lacking PorA bound significantly less C4bp. Increased binding was observed under hypotonic conditions. Deleting PorB3 did not influence C4bp binding, but the presence of polysialic acid capsule reduced C4bp binding by 50%. Bound C4bp remained functionally active in that it promoted the inactivation of C4b by factor I. PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation.

show abstract

Section: Discussionmentioning

confidence: 99%

Binding of the Complement Inhibitor C4bp to Serogroup BNeisseria meningitidis

Jarva

Ram

Vogel

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Neuraminidase treatment of antigens on EIA plates was done essentially as described previously (19)(20)(21). The EIA plates were coated with LPS (25 g/ml of PBS) or with 100 l of a bacterial suspension (unheated; A 595 ϭ 0.2) in PBS.…”

Section: Ii) De-o N Acylation Of Lps By Strong Alkali Treatment (Ps-mentioning

confidence: 99%

Monoclonal antibodies againstHaemophilus ducreyi lipooligosaccharide and their diagnostic usefulness

Ahmed

Borrelli

Jonasson

et al. 1995

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

View full text Add to dashboard Cite

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.

show abstract

“…This tetraose is the carbohydrate moiety also found in a human glycosphingolipid, paragloboside (8,11). Furthermore, in vitro experiments showed that gonococci utilize exogenous cytidine monophospho-N-acetylneuraminic acid and sialylate their LOS (17). As a result of sialylation, gonococci become resistant to complement-mediated killing (15,16).…”

mentioning

confidence: 99%

“…In addition to complex LOS expression, studies by us and others (8,11) have shown that gonococci may mimic human glycolipids or may change serum sensitivity by modifying their LOS (15)(16)(17). The 4.5-kDa LOS produced by strain F62 contains a lactoneotetraose moiety that is linked to the Hep [1] residue of the core trisaccharide as described above (11).…”

mentioning

confidence: 99%