This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kulshin, V A Articles by Rietschel, E T Search for Related Content PubMed PubMed Citation Articles by Kulshin, V A Articles by Rietschel, E T

research-article

Structural characterization of the lipid A component of pathogenic Neisseria meningitidis.

Forschungsinstitut Borstel, Institut für Experimentelle Biologie und Medizin, Germany.

ABSTRACT

The lipid A component of meningococcal lipopolysaccharide was structurally characterized by using chemical modification methods, methylation analysis, 31P nuclear magnetic resonance, and laser desorption mass spectroscopy. It was shown that Neisseria meningitidis lipid A consists of a 1,4'-bisphosphorylated beta(1'----6)-linked D-glucosamine disaccharide (lipid A backbone), both phosphate groups being largely replaced by O-phosphorylethanolamine. This disaccharide harbors two nonsubstituted hydroxyl groups at positions 4 and 6', the latter representing the attachment site of the oligosaccharide portion in lipopolysaccharide. In addition, it is substituted by up to six fatty acid residues. In the major lipid A component, representing a hexaacyl species, the hydroxyl groups at positions 3 and 3' carry (R)-3-hydroxydodecanoic acid [12:0(3-OH)], whereas the amino groups at positions 2 and 2' are substituted by (R)-3-(dodecanoyloxy)tetradecanoic acid [3-O(12:0)-14:0]. A minor portion was present as a tetraacyl lipid A component lacking either dodecanoic acid (12:0) or 12:0 and 12:0(3-OH). N. meningitidis lipid A, therefore, significantly differs from Escherichia coli lipid A by the nature and locations of fatty acids and the substitution of O-phosphorylethanolamine for the nonglycosyl (4'-P) and glycosyl phosphate.

This article has been cited by other articles:

• Steeghs, L., Keestra, A. M., van Mourik, A., Uronen-Hansson, H., van der Ley, P., Callard, R., Klein, N., van Putten, J. P. M. (2008). Differential Activation of Human and Mouse Toll-Like Receptor 4 by the Adjuvant Candidate LpxL1 of Neisseria meningitidis. Infect. Immun. 76: 3801-3807 [Abstract] [Full Text]  
• Naessan, C. L., Egge-Jacobsen, W., Heiniger, R. W., Wolfgang, M. C., Aas, F. E., Rohr, A., Winther-Larsen, H. C., Koomey, M. (2008). Genetic and Functional Analyses of PptA, a Phospho-Form Transferase Targeting Type IV Pili in Neisseria gonorrhoeae. J. Bacteriol. 190: 387-400 [Abstract] [Full Text]  
• Tran, A. X., Whittimore, J. D., Wyrick, P. B., McGrath, S. C., Cotter, R. J., Trent, M. S. (2006). The Lipid A 1-Phosphatase of Helicobacter pylori Is Required for Resistance to the Antimicrobial Peptide Polymyxin.. J. Bacteriol. 188: 4531-4541 [Abstract] [Full Text]  
• Lukasiewicz, J., Niedziela, T., Jachymek, W., Kenne, L., Lugowski, C. (2006). Structure of the lipid A-inner core region and biological activity of Plesiomonas shigelloides O54 (strain CNCTC 113/92) lipopolysaccharide. Glycobiology 16: 538-550 [Abstract] [Full Text]  
• Post, D. M.B., DeSheng Zhang, , Weiss, J. P., Gibson, B. W. (2006). Stable isotope metabolic labeling of Neisseria meningitidis lipooligosaccharide. Innate Immunity 12: 93-98 [Abstract]  
• Plant, L., Sundqvist, J., Zughaier, S., Lovkvist, L., Stephens, D. S., Jonsson, A.-B. (2006). Lipooligosaccharide Structure Contributes to Multiple Steps in the Virulence of Neisseria meningitidis. Infect. Immun. 74: 1360-1367 [Abstract] [Full Text]  
• Rustam, T., McClean, S., Newcombe, J., McFadden, J., Eales-Reynolds, L.-J. (2006). Reduced toxicity of lipo-oligosaccharide from a phoP mutant of Neisseria meningitidis: an in vitro demonstration. Innate Immunity 12: 39-46 [Abstract]  
• Zhu, P., Boykins, R. A., Tsai, C.-M. (2006). Genetic and functional analyses of the lgtH gene, a member of the {beta}-1,4-galactosyltransferase gene family in the genus Neisseria. Microbiology 152: 123-134 [Abstract] [Full Text]  
• Gangloff, S. C., Zahringer, U., Blondin, C., Guenounou, M., Silver, J., Goyert, S. M. (2005). Influence of CD14 on Ligand Interactions between Lipopolysaccharide and Its Receptor Complex. J. Immunol. 175: 3940-3945 [Abstract] [Full Text]  
• Fisseha, M., Chen, P., Brandt, B., Kijek, T., Moran, E., Zollinger, W. (2005). Characterization of Native Outer Membrane Vesicles from lpxL Mutant Strains of Neisseria meningitidis for Use in Parenteral Vaccination. Infect. Immun. 73: 4070-4080 [Abstract] [Full Text]  
• Tran, A. X., Karbarz, M. J., Wang, X., Raetz, C. R. H., McGrath, S. C., Cotter, R. J., Trent, M. S. (2004). Periplasmic Cleavage and Modification of the 1-Phosphate Group of Helicobacter pylori Lipid A. J. Biol. Chem. 279: 55780-55791 [Abstract] [Full Text]  
• Phillips, N. J., Schilling, B., McLendon, M. K., Apicella, M. A., Gibson, B. W. (2004). Novel Modification of Lipid A of Francisella tularensis. Infect. Immun. 72: 5340-5348 [Abstract] [Full Text]  
• Steeghs, L., Tommassen, J., Leusen, J. H.W., van de Winkel, J. G.J., van der Ley, P. (2004). Teasing apart structural determinants of `toxicity' and `adjuvanticity': implications for meningococcal vaccine development. Innate Immunity 10: 113-119 [Abstract]  
• Sprong, T., Netea, M. G., van der Ley, P., Verver-Jansen, T. J. G., Jacobs, L. E. H., Stalenhoef, A., van der Meer, J. W. M., van Deuren, M. (2004). Human lipoproteins have divergent neutralizing effects on E. coli LPS, N. meningitidis LPS, and complete Gram-negative bacteria. J. Lipid Res. 45: 742-749 [Abstract] [Full Text]  
• Nikaido, H. (2003). Molecular Basis of Bacterial Outer Membrane Permeability Revisited. Microbiol. Mol. Biol. Rev. 67: 593-656 [Abstract] [Full Text]  
• Pridmore, A. C., Jarvis, G. A., John, C. M., Jack, D. L., Dower, S. K., Read, R. C. (2003). Activation of Toll-Like Receptor 2 (TLR2) and TLR4/MD2 by Neisseria Is Independent of Capsule and Lipooligosaccharide (LOS) Sialylation but Varies Widely among LOS from Different Strains. Infect. Immun. 71: 3901-3908 [Abstract] [Full Text]  
• Cox, A. D., Wright, J. C., Li, J., Hood, D. W., Moxon, E. R., Richards, J. C. (2003). Phosphorylation of the Lipid A Region of Meningococcal Lipopolysaccharide: Identification of a Family of Transferases That Add Phosphoethanolamine to Lipopolysaccharide. J. Bacteriol. 185: 3270-3277 [Abstract] [Full Text]  
• Post, D. M. B., Ketterer, M. R., Phillips, N. J., Gibson, B. W., Apicella, M. A. (2003). The msbB Mutant of Neisseria meningitidis Strain NMB Has a Defect in Lipooligosaccharide Assembly and Transport to the Outer Membrane. Infect. Immun. 71: 647-655 [Abstract] [Full Text]  
• Tzeng, Y.-L., Datta, A., Kolli, V. K., Carlson, R. W., Stephens, D. S. (2002). Endotoxin of Neisseria meningitidis Composed Only of Intact Lipid A: Inactivation of the Meningococcal 3-Deoxy-D-Manno-Octulosonic Acid Transferase. J. Bacteriol. 184: 2379-2388 [Abstract] [Full Text]  
• Brandtzaeg, P., Bjerre, A., Ovstebo, R., Brusletto, B., Joo, G. B., Kierulf, P. (2001). Invited review: Neisseria meningitidis lipopolysaccharides in human pathology. Innate Immunity 7: 401-420 [Abstract]  
• van der Ley, P., Steeghs, L., Hamstra, H. J., ten Hove, J., Zomer, B., van Alphen, L. (2001). Modification of Lipid A Biosynthesis in Neisseria meningitidis lpxL Mutants: Influence on Lipopolysaccharide Structure, Toxicity, and Adjuvant Activity. Infect. Immun. 69: 5981-5990 [Abstract] [Full Text]  
• Rahman, M. M., Kahler, C. M., Stephens, D. S., Carlson, R. W. (2001). The structure of the lipooligosaccharide (LOS) from the {alpha}-1,2-N-acetyl glucosamine transferase (rfaKNMB) mutant strain CMK1 of Neisseria meningitidis: implications for LOS inner core assembly and LOS-based vaccines. Glycobiology 11: 703-709 [Abstract] [Full Text]  
• Alexander, C., Rietschel, E. Th. (2001). Invited review: Bacterial lipopolysaccharides and innate immunity. Innate Immunity 7: 167-202 [Abstract]  
• Koyama, S., Sato, E., Nomura, H., Kubo, K., Miura, M., Yamashita, T., Nagai, S., Izumi, T. (2000). The potential of various lipopolysaccharides to release IL-8 and G-CSF. Am. J. Physiol. Lung Cell. Mol. Physiol. 278: L658-L666 [Abstract] [Full Text]  
• Griffiss, J. M., Brandt, B. L., Saunders, N. B., Zollinger, W. (2000). Structural Relationships and Sialylation among Meningococcal L1, L8, and L3,7 Lipooligosaccharide Serotypes. J. Biol. Chem. 275: 9716-9724 [Abstract] [Full Text]  
• Wyckoff, T. J.O., Shanhua Lin, , Cotter, R. J., Dotson, G. D., Raetz, C. R.H. (1999). Acyl chain length specificity of UDP-N-acetylglucosamine 3-O-acyltransferases. Innate Immunity 5: 179-180  
• Schromm, A. B., Brandenburg, K., Loppnow, H., Zahringer, U., Rietschel, E. Th., Carroll, S. F., Koch, M. H. J., Kusumoto, S., Seydel, U. (1998). The Charge of Endotoxin Molecules Influences Their Conformation and IL-6-Inducing Capacity. J. Immunol. 161: 5464-5471 [Abstract] [Full Text]  
• Odegaard, T. J., Kaltashov, I. A., Cotter, R. J., Steeghs, L., van der Ley, P., Khan, S., Maskell, D. J., Raetz, C. R. H. (1997). Shortened Hydroxyacyl Chains on Lipid A of Escherichia coli Cells Expressing a Foreign UDP-N-Acetylglucosamine O-Acyltransferase. J. Biol. Chem. 272: 19688-19696 [Abstract] [Full Text]  
• Velucchi, M., Rustici, A., Meazza, C., Villa, P., Ghezzi, P., Tsai, C-M., Porro, M. (1997). A model of Neisseria meningitidis vaccine based on LPS micelles detoxified by synthetic antiendotoxin peptides. Innate Immunity 4: 261-272 [Abstract]  
• Giardina, P. C., Gioannini, T., Buscher, B. A., Zaleski, A., Zheng, D.-S., Stoll, L., Teghanemt, A., Apicella, M. A., Weiss, J. (2001). Construction of Acetate Auxotrophs of Neisseria meningitidis to Study Host-Meningococcal Endotoxin Interactions. J. Biol. Chem. 276: 5883-5891 [Abstract] [Full Text]