Endogenous sialylation of the lipooligosaccharides of Neisseria meningitidis

Mandrell, Robert E.; Kim, J J; John, Constance M.; Gibson, Brad; Sugai, James V.; Apicella, Michael A.; Griffiss, J M; Yamasaki, Ryohei

doi:10.1128/jb.173.9.2823-2832.1991

Cited by 133 publications

(142 citation statements)

References 63 publications

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“…A 1D-TOCSY experiment by irradiation of H1 of the A-D-Gal residue gave scalar connectivities up to H4 (Fig. 4 e), gion 50Ϫ60 ppm in an 1 H-13 C HMQC experiment confirmed the assignment of the spin-systems arising from these GlcN residues while correlation beyond H4 to H5 was not observed due to the very small 3 J 4,5 coupling (Ͻ1 Hz) [28]. Distinctions between the as well as the A-GlcN in the inner core region of the molecule.…”

Section: Glycosyl Linkage Analysis Methylation Analysis Data For Thementioning

confidence: 82%

Structure of an α‐2,6‐sialylated lipooligosaccharide from Neisseria meningitidis immunotype L1

Wakarchuk

Gilbert

Martin

et al. 1998

European Journal of Biochemistry

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The recent cloning of the lipooligosaccharide (LOS) A-2,3-sialyltransferase from Neisseria meningitidis immunotype L3 permitted us to examine other immunotypes for this structural gene. We identified the gene and measured the enzyme activity in the L1 immunotype strain which had previously been reported to lack sialic acid in its LOS because it contains a terminal A-linked galactose which was thought not to be an acceptor for the sialyltransferase. This finding prompted us to re-examine the structure of the LOS from the L1 immunotype, which revealed the presence of sialic acid on the terminal A-linked galactose. Oligosaccharides derived from the LOS were shown to be sialylated by composition and methylation analysis, mass spectrometry and nuclear magnetic resonance. The detailed structural analysis showed the sialic acid to occur only at O6 of the teminal A-D-galactopyranose residue of the A-D-Gal-1,4-β-D-Gal-1,4-β-D-glc trisaccharide (P k epitope) chain of the LOS, in the A-D configuration. These data are the first report of a A-2,6-linked sialic acid in a bacterial LOS or lipopolysaccharide, and also the first report of a sialylated P k epitope.Keywords : sialyltransferase ; Neisseria meningitidis; glycosyltransferase; lipooligosaccharide.The A-2,3-sialyltransferase involved in the biosynthesis of The mucosal pathogens in the genera Neisseria, Haemophilus, Moraxella, Campylobacter and Bordetella all possess a ma-sialyllacto-N-neotetraose has been reported to occur in the major cell surface lipooligosaccharide (LOS) which has features jority of the N. meningitidis immunotypes as well as N. gonorthat distinguish it from the enterobacterial lipopolysaccharide rhoeae isolates [8]. The distibution of enzyme activity does not (LPS) [1]. Perhaps the most important distinction is that struc-always correlate with the presence or absence of lacto-N-neotures displayed in LOS from these bacteria have some structural tetraose in the LOS. We previously reported that the N. meninsimilarity to human glycolipids. The LOS molecules elaborated gitidis A-2,3-sialyltransferase has a relaxed acceptor specificity by strains of N. meningitidis and N. gonorrhoeae that have been in that it would use synthetic acceptors which presented terminal shown to be important in the disease mechanism include those N-acetyllactosamine, lactose or galactose [9]. We have extended presenting the following oligosaccharide structures: Lacto-N-our examination of this enzyme and have reported recently that neotetraose, Sialyllacto-N-neotetraose, and the P k blood group the A-2,3-sialyltransferase from N. meningitidis immunotypes L3 antigen [1] (Fig. 1). These oligosaccharides provide these patho-and L1 can also use the terminal A-D-galactose, to make an Agens with a means of evading the host immune response through 2,3-sialyl-P k -trisaccharide in vitro with a synthetic acceptor molmolecular mimicry and are therefore potent virulence factors [2]. ecule [10]. Since we had demonstrated that an A-D-galactose resThe genetics of LPS biosynthesis have been ext...

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Section: Glycosyl Linkage Analysis Methylation Analysis Data For Thementioning

confidence: 82%

Structure of an α‐2,6‐sialylated lipooligosaccharide from Neisseria meningitidis immunotype L1

Wakarchuk

Gilbert

Martin

et al. 1998

European Journal of Biochemistry

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“…A potential disadvantage of this type of approach is the loss of more labile substituents, for example, sialic acid, which can be cleaved by mild acid hydrolysis procedures used to cleave the Kdo moiety linking the OS and LA. In the past, we have O-deacylated the LOS to prevent losses from acid hydrolysis and to increase solubility and detection in liquid secondary ion (19,43), electrospray, and MALDI mass spectrometry (33). Challenges in mass spectrometric analysis of mixtures include the relationship between detection sensitivity and Figure 2A and is presented for comparison.…”

Section: Discussionmentioning

confidence: 99%

“…Native or intact LOS was O-deacylated prior to MS analysis as reported previously (19). Briefly, LOS (?0.3 mg) was placed in a 1.5 ml polypropylene tube, and 200 ml of anhydrous hydrazine was added.…”

Section: O-deacylation Of Native Losmentioning

confidence: 99%

Profiles of structural heterogeneity in native lipooligosaccharides of Neisseria and cytokine induction

John

Liu

Jarvis

2009

Journal of Lipid Research

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Fine differences in the phosphorylation and acylation of lipooligosaccharide (LOS) from Neisseria species are thought to profoundly influence the virulence of the organisms and the innate immune responses of the host, such as signaling through toll-like receptor 4 (TLR4) and triggering receptor expressed on myeloid cells (TREM). MALDI time-of-flight (TOF) mass spectrometry was used to characterize heterogeneity in the native LOS from Neisseria gonorrheae and N. meningitidis. A sample preparation methodology previously reported for Escherichia coli lipopolysaccharide (LPS) employing deposition of untreated LOS on a thin layer of a film composed of 2,4,6-trihydroxyacetophenone and nitrocellulose was used. Prominent peaks were observed corresponding to molecular ions and to fragment ions primarily formed by cleavage between the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) and the lipid A (LA). Analyses of these data and comparison with spectra of the corresponding Odeacylated or hydrogen fluoride-treated LOS enabled the detection of novel species that apparently differed by the expression of up to three phosphates with one or more phosphoethanolamine (PEA) groups on the LA. We found that the heterogeneity profile of acylation and phosphorylation correlates with the induction of proinflammatory cytokines in THP-1 monocytic cells. This methodology enabled us to rapidly profile components of structural variants of native LOS that are of importance biologically.-John, C. M., M. Liu, and G. A. Jarvis. Profiles of structural heterogeneity in native lipooligosaccharides of Neisseria and cytokine induction. J. Lipid Res. 2009. 50: 424-438. Supplementary key words lipooligosaccharideThe lipooligosaccharide (LOS) of Neisseria gonorrheae and N. meningitidis is structurally related to the lipopolysaccharide (LPS) of enteric Gram-negative bacteria but does not have repeating O-antigens (1). LOS and LPS have conserved inner cores composed of L-glycero-D-manno-heptose (Hep) and 3-deoxy-D -manno-oct-2-ulosonic acid (Kdo), which are anchored in the outer membrane by lipid A (LA). The structure of the LA of gonococci and meningococci, although based on a limited number of studies, generally differs from that of Escherichia coli in the acylation and the chain length of the fatty acid residues. With regard to phosphorylation, a limited number of studies have shown that gonococci and meningococci elaborate LOS containing a LA, which is phosphorylated with variable numbers of phosphate (P) and phosphoethanolamine (PEA) residues. The recent report of a PEA transferase specific for the LA on meningococcal LOS creates the possibility of phase variation in phosphorylation (2). Thus, the LA expressed by these organisms exhibit heterogeneity in acylation and phosphorylation, both of which have been shown to influence the endotoxicity in E. coli LPS (3).The innate immune response to bacterial pathogens relies on the detection of pathogen-associated molecular patterns by pattern recognition molecules. Toll-like receptor 4 (TLR4) is one of...

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“…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.

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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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Endogenous sialylation of the lipooligosaccharides of Neisseria meningitidis

Cited by 133 publications

References 63 publications

Structure of an α‐2,6‐sialylated lipooligosaccharide from Neisseria meningitidis immunotype L1

Structure of an α‐2,6‐sialylated lipooligosaccharide from Neisseria meningitidis immunotype L1

Profiles of structural heterogeneity in native lipooligosaccharides of Neisseria and cytokine induction

Monoclonal antibodies againstHaemophilus ducreyi lipooligosaccharide and their diagnostic usefulness

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