Meningococcal lipopolysaccharides: virulence factor and potential vaccine component.

Verheul, A. F. M.; Snippe, H.P.; Poolman, Jan

doi:10.1128/mmbr.57.1.34-49.1993

Cited by 65 publications

(48 citation statements)

References 93 publications

(239 reference statements)

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“…It would seem prudent to take the observations presented in our study into account when designing experiments which utilize PCR amplification of homopolymeric tracts. Verheul et al (1993) have proposed that meningococcal LPS has potential as a vaccine candidate, but the presence of galactose-containing structures, such as Galcz(1-4)13Gal and lacto-N-neotetraose, could lead to immunopathology due to cross-reactivity with similar human structures. This problem has been addressed by the use of gale mutant strains which synthesize a truncated LPS that lacks the terminal region entirely (see Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Meningococcal meningitis and septicaemia remain as significant health problems worldwide. The lipopolysaccharide (LPS) of Neisseria meningitidis (Nm) is known to be a major determinant of virulence (Jones et al, 1992), and the use of monoclonal antibodies and structural studies have demonstrated the heterogeneity and complexity of meningococcal LPS which can be divided into 12 immunotypes (ITs; Verheul et al, 1993). Present in neisserial LPS are the terminal structures, Gal=(1-4)13Gal and lacto-Nneotetraose, which are also found on the surface of human epithelial cells or in host secretions Virji et aL, 1990); the presence of these structures in LPS may facilitate the evasion of the host immune system.…”

Section: Introductionmentioning

confidence: 99%

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Molecular analysis of a locus for the biosynthesis and phase‐variable expression of the lacto‐N‐neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis

Jennings

Hood

Peak

et al. 1995

Molecular Microbiology

184

178

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Lipopolysaccharide (LPS) is a major determinant of Neisseria, meningitidis virulence. A key feature of meningococcal LPS is the phase-variable expression of terminal structures which are proposed to have disparate roles in pathogenesis. In order to identify the biosynthetic genes for terminal LPS structures and the control mechanisms for their phase-variable expression, the lic2A gene, which is involved in LPS biosynthesis in Haemophilus influenzae, was used as a hybridization probe to identify a homologous gene in N. meningitidis strain MC58. The homologous region of DNA was cloned and nucleotide sequence analysis revealed three open reading frames (ORFs), two of which were homologous to the H. influenzae lic2A gene. All three ORFs were mutagenized by the insertion of antibiotic-resistance cassettes and the LPS from these mutant strains was analysed to determine if the genes had a role in LPS biosynthesis. Immunological and tricine-SDS-PAGE analysis of LPS from the mutant strains indicated that all three genes were probably transferases in the biosynthesis of the terminal lacto-N-neotetraose structure of meningococcal LPS. The first ORF of the locus contains a homopolymeric tract of 14 guanosine residues within the 5'-end of the coding sequence. As the lacto-N-neotetraose structure in meningococcal LPS is subject to phase-variable expression, colonies that no longer expressed the terminal structure, as determined by monoclonal antibody binding, were isolated. Analysis of an 'off' phase variant revealed a change in the number of guanosine residues resulting in a frameshift mutation, indicating that a slipped-strand mispairing mechanism, operating in the first ORF, controls the phase-variable expression of lacto-N-neotetraose.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular analysis of a locus for the biosynthesis and phase‐variable expression of the lacto‐N‐neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis

Jennings

Hood

Peak

et al. 1995

Molecular Microbiology

184

178

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“…In contrast to this, only little is known about the role of the LPS carbohydrate structure in N. meningitidis pathogenesis. However, the use of truncated LPS isoforms for vaccination is an area of immense interest (Verheul et al ., 1993;Li et al ., 2004). For these reasons, the function of the LPS carbohydrate moiety in the interaction of N. meningitidis with human DC is addressed in this study.…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate composition of meningococcal lipopolysaccharide modulates the interaction of Neisseria meningitidis with human dendritic cells

Kurzai

Schmitt

Claus

et al. 2005

Cellular Microbiology

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Summary Meningococcal lipopolysaccharide (LPS) is of crucial importance for the pathogenesis of invasive infection.We show that sialylation and elongation of the alphachain effectively shields viable unencapsulated Neisseria meningitidis from recognition by human dendritic cells (DC). In contrast, beta-and gammachain of the LPS carbohydrate moiety play only a minor role in the interaction with DC. The protective function of the LPS for the bacteria can be counteracted in vivo by phase variation of the lgtA gene encoding LPS glycosyltransferase A. Capsule expression protects N. meningitidis efficiently from recognition and phagocytosis by DC independent of the LPS structure. Despite the significant impact of LPS composition on the adhesion and phagocytosis of N. meningitidis no differences were found in terms of cytokine levels secreted by DC for IL1-beta, IL-6, IL-8, TNF-alpha, IFN-gamma and GM-CSF. However, significantly lower levels of the regulatory mediator IL-10 were induced by encapsulated strains in comparison to isogenic unencapsulated derivatives. IL-10 secretion was shown to depend on phagocytosis because poly alpha-2,8 sialic acid did not influence IL-10 secretion. The use of truncated LPS isoforms in vaccine preparations can therefore not only result in attenuation but also in more efficient targeting of DC.

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“…The meningococcal outer membrane lipooligosaccharide (NmLOS) has also been proposed as a vaccine candidate, but the presence of sugars that mimic human antigens which can be endogenously sialylated [8] and the endotoxin lipid A also raises serious concerns about its safety [9,10]. Nevertheless, NmLOS has epitopes that are immunogenic in infants and children [11,12].…”

Section: Introductionmentioning

confidence: 99%

Peptide mimics elicit antibody responses against the outer-membrane lipooligosaccharide of group B Neisseria meningitidis

Charalambous

2000

FEMS Microbiology Letters

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As an alternative approach towards the development of a meningococcal vaccine, the potential of peptide mimics of lipooligosaccharide (LOS) to elicit cross-reactive immune responses against LOS was investigated. The heptapeptides SMYGSYN and APARQLP were identified by enrichment from a coliphage display library with a LOS-specific monoclonal antibody. Mice immunised with these peptides conjugated to diphtheria toxoid elicited a total IgG response to LOS with geometric mean titres 2^4 times higher compared with nonimmunised controls. There was an increase in LOS-specific IgG1 immunoglobulin, whereas specific IgG2a and IgG3 decreased slightly in response to immunisation. The data demonstrated that peptide mimics can elicit immune responses against meningococcal LOS. ß

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Meningococcal lipopolysaccharides: virulence factor and potential vaccine component.

Cited by 65 publications

References 93 publications

Molecular analysis of a locus for the biosynthesis and phase‐variable expression of the lacto‐N‐neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis

Molecular analysis of a locus for the biosynthesis and phase‐variable expression of the lacto‐N‐neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis

Carbohydrate composition of meningococcal lipopolysaccharide modulates the interaction of Neisseria meningitidis with human dendritic cells

Peptide mimics elicit antibody responses against the outer-membrane lipooligosaccharide of group B Neisseria meningitidis

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