Abstract

Lipid A, a constituent of the outer membrane of gram-negative bacteria, is a structurally unique molecule that does not exist in animal cells. The lipid A of most gram-negative bacteria is structurally similar, with analogous biosynthetic steps. These facts, combined with the fact that lipid A is required for the survival of most, if not all gram-negative bacteria, make lipid A biosynthesis an excellent target for antibiotics.

Keywords

Sugar Pseudomonas Oligosaccharide Galactose Erythromycin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Aasland, R., J. Coleman, A.L. Hoick, C. Smith, C.R.H. Raetz, and K. Kleppe. 1988. The 17K protein, a DNA-binding protein from Escherichia coli is identical to the firA gene product. J. Bacteriol. 170:5916–5918.PubMedGoogle Scholar
  2. 2.
    Anderson, M.S., C.E. Bulawa, and C.R.H. Raetz. 1985. The biosynthesis of gram-negative endotoxin: formation of lipid A precursors from UDP-G1cNAc in extracts of Escherichia coli. J. Biol. Chem. 260:15536–15541.PubMedGoogle Scholar
  3. 3.
    Anderson, M.S., and C.R.H. Raetz. 1987. Biosynthesis of lipid A precursors in Escherichia coli: A cytoplasmic acyltransferase that converts UDP-N-acetylglucosamine to UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine. J. Biol. Chem. 262:5159–5169.PubMedGoogle Scholar
  4. 4.
    Anderson, M.S., A.D. Robertson, I. Macher, and C.R.H. Raetz. 1988. Biosynthesis of lipid A in Escherichia coli: Identification of UDP-3-O-[(R)-3-hydroxymyristoyl]a-D-glucosamine as a precursor of UDP-N203-bis[(R)-3-hydroxymyristoyl]-a-D-glucosamine. Biochemistry. 27:1908–1917.PubMedCrossRefGoogle Scholar
  5. 5.
    Benson, S.A., J.L. Occi, and B.A. Sampson. 1988. Mutations that alter the pore function of the OmpF porin of Escherichia coli K12. J. Mol. Biol. 203:961–970.PubMedCrossRefGoogle Scholar
  6. 6.
    Bligh, E., and W.J. Dyer. 1959. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37:911–917.PubMedCrossRefGoogle Scholar
  7. 7.
    Brozek, K.A., K. Hosaka, A.D. Robertson, and C.R. Raetz. 1989. Biosynthesis of lipopolysaccharide in Escherichia coli: Cytoplasmic enzymes that attach 3-deoxy-Dmanno-octulosonic acid to lipid A. J. Biol. Chem. 264:6956–6966.PubMedGoogle Scholar
  8. 8.
    Brozek, K.A., and C.R.H. Raetz. 1990. Biosynthesis of lipid A in Escherichia coli: Acyl carrier protein-dependent incorporation of laurate and myristate. J. Biol. Chem. 265:15410–15417.PubMedGoogle Scholar
  9. 9.
    Bulawa, C.E., and C.R.H. Raetz. 1984. The biosynthesis of gram-negative endotoxin: identification and function of UDP-diacylglucosamine in Escherichia coli. J. Biol. Chem. 259:4846–4851.PubMedGoogle Scholar
  10. 10.
    Claesson, A., A.M. Jansson, B.G. Pring, S.M. Hammond, and B. Ekström. 1987. Design and synthesis of peptide derivatives of a 3-deoxy-D-manno-2-octulosonic acid (KDO) analogue as novel antibacterial agents acting upon lipopolysaccharide biosynthesis. J. Med. Chem. 30:2309–2313.PubMedCrossRefGoogle Scholar
  11. 11.
    Clementz, T., and C.R.H. Raetz. 1991. A gene coding for 3-deoxy-D-manno-actulosonic-acid transferase in Escherichia coli: identification, mapping, cloning, and sequencing. J. Biol. Chem. 266:9687–9696.PubMedGoogle Scholar
  12. 12.
    Coleman, J., and C.R.H. Raetz. 1988. The first committed step of lipid A biosynthesis in Escherichia coli: Sequence of the 1pxA gene. J. Bacteriol. 170:1268–1274.PubMedGoogle Scholar
  13. 13.
    Coleman, J., and C.R.H. Raetz. 1988. Transcriptional analysis of the 1px operon of Escherichia coli: Evidence for in vivo coupling with dnaE. The FASEB J. 2:a1371-a1371.Google Scholar
  14. 14.
    Cotter, R.J., J. Honovich, N. Qureshi, and K. Takayama. 1987. Structural determination of lipid A from gram negative bacteria using laser desorption mass spectrometry. Biomed. Environ. Mass. Spectrom. 14:591–598.PubMedCrossRefGoogle Scholar
  15. 15.
    Crowell, D.N., M.S. Anderson, and C.R.H. Raetz. 1986. Molecular cloning of the genes for lipid A disaccharide synthase and UDP-N-acetylglucosamine acyltransferase in Escherichia coli. J. Bacteriol. 168:152–159.PubMedGoogle Scholar
  16. 16.
    Crowell, D.N., W.S. Reznikoff, and C.R.H. Raetz. 1987. Nucleotide sequence of the Escherichia coli gene for lipid A disaccharide synthase. J. Bacteriol. 169:57275734.PubMedGoogle Scholar
  17. 17.
    Galanos, C., O. Luderitz, E.T. Rietschel, and O. Westphal. 1977. Newer aspects of the chemistry and biology of bacterial lipopolysaccharides with special reference to their lipid A component, p. 239–335. In T.W. Goodwin (ed.), International review of biochemistry: biochemistry of lipids II, vol. 14. University Park Press, Baltimore.Google Scholar
  18. 18.
    Galloway, S.M., and C.R.H. Raetz. 1990. A mutant of Escherichia coli defective in the first step of endotoxin biosynthesis. J. Biol. Chem. 265:6394–6402.PubMedGoogle Scholar
  19. 19.
    Goldman, R., W. Kohlbrenner, P. Lartey, and A. Pernet. 1987. Antibacterial agents specifically inhibiting lipopolysaccharide synthesis. Nature 329:162–164.PubMedCrossRefGoogle Scholar
  20. 20.
    Goldman, R.C., T.J. Bolling, W.E. Kohlbrenner, Y. Kim, and J.L. Fox. 1986. Primary structure of CTP:CMP-3-deoxy-D-manno-octulosonate cytidyly transferase (CMP-KDO synthetase) from Escherichia coli. J. Biol. Chem. 261:15831–15835.PubMedGoogle Scholar
  21. 21.
    Goldman, R.C., C.C. Doran, S.K. Kadam, and J.O. Capobianco. 1988. Lipid A precursor from Pseudomonas aeruginosa is completely acylated prior to addition of 3-deoxy-D-manno-octulosonate. J. Biol. Chem. 263:5217–5223.PubMedGoogle Scholar
  22. 22.
    Hammond, S.M., A. Claesson, A.M. Jansson, L.-G. Larsson, B.G. Pring, C.M. Town, and B. Ekström. 1987. A new class of synthetic antibacterials acting on lipopolysaccharide biosynthesis. Nature 327:730–732.PubMedCrossRefGoogle Scholar
  23. 23.
    Hirota, Y., H. Suzuki, Y. Nishimura, and S. Yasuda. 1977. On the process of cellular division in Escherichia coli: a mutant of E. coli lacking a murein-lipoprotein. Proc. Natl. Acad. Sci. U.S.A. 74:1417–1420.PubMedCrossRefGoogle Scholar
  24. 24.
    Hirvas, L., J. Coleman, P. Koski, and M. Vaara. 1990. Bacterial “histone-like protein I” (HLP-I) is an outer membrane constituent? FEBS. Lett. 262:122–126.CrossRefGoogle Scholar
  25. 25.
    Högenauer, G., and M. Woisetschläger. 1981. A diazaborine derivative inhibits lipopolysaccharide biosynthesis. Nature 293:662–664.PubMedCrossRefGoogle Scholar
  26. 26.
    Ichimura, M., T. Koguchi, T. Yasuzawa, and F. Tomita. 1987. CV-1, a new antibiotic produced by a strain of Streptomyces sp.: I. Fermentation, isolation and biological properties of the antibiotic. J. Antibiotics 40:723–726.CrossRefGoogle Scholar
  27. 27.
    Ishiguro, E.E., D. Vanderwel, and W. Kusser. 1986. Control of lipopolysaccharide biosynthesis and release by Escherichia coli and Salmonella typhimurium. J. Bacteriol. 168:328–333.PubMedGoogle Scholar
  28. 28.
    Kasai, N., S. Arata, J. Mashimo, Y. Akiyama, C. Tanaka, K. Egawa, and S. Tanaka. 1987. Pseudomonas diminuta LPS with a new endotoxic lipid A structure. Biochem. Biophys. Res. Commun. 142:972–978.PubMedCrossRefGoogle Scholar
  29. 29.
    Kohlbrenner, W.E., and S.W. Fesik. 1985. Determination of the anomeric specificity of the Escherichia coli CTP:CMP-3-deoxy-n-manno-octulosonate cytidylyltransferase by13C NMR spectroscopy. J. Biol. Chem. 260:14695–14700.PubMedGoogle Scholar
  30. 30.
    Kohlbrenner, W.E., Nuss M.M., and Fesik S.W.. 1987.31P and13C NMR studies of oxygen transfer during catalysis by 3-deoxy-D-manno-octulosonate cytidylyltransferase from Escherichia coli. J. Biol. Chem. 262:4534–4537.PubMedGoogle Scholar
  31. 31.
    Koski, P., M. Rhen, J. Kantele, and M. Vaara. 1989. Isolation, cloning, and primary structure of a cationic 16-kDa outer membrane protein of Salmonella typhimurium. J. Biol. Chem. 264:18973–18980.PubMedGoogle Scholar
  32. 32.
    Krauss, J.H., U. Seydel, J. Weckesser, and H. Mayer. 1989. Structural analysis of the nontoxic lipid A of Rhodobacter capsulatus 37b4 Eur. J. Biochem. 180:519526.PubMedCrossRefGoogle Scholar
  33. 33.
    Lancy, E.D., M.R. Lifsics, P. Munson, and R. Maurer. 1989. Nucleotide sequences of dnaE the gene for the polymerase subunit of DNA polymerase III in Salmonella typhimurium and a variant that facilitates growth in the absence of another polymerase subunit. J. Bacteriol. 171:5581–5586.PubMedGoogle Scholar
  34. 34.
    Lathe, R., H. Buc, J.-P. Lecocq, and E.K.F. Bautz. 1980. Prokaryotic histone-like protein interacting with RNA polymerase. Proc. Natl. Acad. Sci. U.S.A. 77:35483552.PubMedCrossRefGoogle Scholar
  35. 35.
    Lathe, R., and J.-P. Lecocq. 1977. ThefirA gene, a locus involved in the expression of rifampicin resistance in Escherichia coli I. Characterization of lambda-firA transducing phages constructed in vitro. Molec. Gen. Genet. 154:43–51.PubMedCrossRefGoogle Scholar
  36. 36.
    Lehmann, V., E. Rupprecht, and M.J. Osborn. 1977. Isolation of mutants conditionally blocked in the biosynthesis of the 3-deoxy-n-manno-octulosonic acid-lipid Apart of lipopolysaccharides derived from Salmonella typhimurium. Eur. J. Biochem. 76:41–49.PubMedCrossRefGoogle Scholar
  37. 37.
    Lindsay, S.S., B. Wheeler, K.E. Sanderson, J.W. Costerton, and K.J. Cheng. 1973. The release of alkaline phosphatase and of lipopolysaccharide during the growth of rough and smooth strains of Salmonella typhimurium. Can. J. Microbiol. 19:335343.Google Scholar
  38. 38.
    Maurer, R., B.C. Osmond, E. Shekhtman, A. Wong, and D. Botstein. 1984. Functional interchangeability of DNA replication genes in Salmonella typhimurium and Escherichia coli demonstrated by a general complementation procedure. Genetics 108:1–23.PubMedGoogle Scholar
  39. 39.
    Morrison, D.C., and J.L. Ryan. 1987. Endotoxins and disease mechanisms. Ann. Rev. Med. 38:417–432.PubMedCrossRefGoogle Scholar
  40. 40.
    Munson, R.S., Jr., N.S. Rasmussen, and M.J. Osborn. 1978. Biosynthesis of lipid A: Enzymatic incorporation of 3-deoxy-D-manno-octulosonate into a precursor of lipid A in Salmonella typhimurium. J. Biol. Chem. 253:1503–1511.PubMedGoogle Scholar
  41. 41.
    Nikaido, H. 1979. Nonspecific transport through the outer membrane, p. 361–401. In M. Inouye (ed.), Bacterial outer membranes. John Wiley and Sons, Inc., New York.Google Scholar
  42. 42.
    Nikaido, H., and M. Vaara. 1987. Outer membrane, p. 7–22. In F.C. Neidhardt (ed.) Escherichia coli and Salmonella typhimurium: cellular and molecular biology, vol. 1. American Society for Microbiology, Washington, D.C.Google Scholar
  43. 43.
    Nishijima, M., C.E. Bulawa, and C.R.H. Raetz. 1981. Two interacting mutations causing temperature-sensitive phosphatidylglycerol synthesis in Escherichia coli membranes. J. Bacteriol. 145:113–121.PubMedGoogle Scholar
  44. 44.
    Nishijima, M., and C.R.H. Raetz. 1979. Membrane lipid biogenesis in Escherichia coli: Identification of genes for phosphatidylglycerophosphate synthetase and construction of mutants lacking phosphatidylglycerol. J. Biol. Chem. 254:7837–7844.PubMedGoogle Scholar
  45. 45.
    Nishijima, M., and C.R.H. Raetz. 1981. Characterization of two membrane-associated glycolipids from an Escherichia coli mutant deficient in phosphatidylglycerol. J. Biol. Chem. 256:10690–10696.PubMedGoogle Scholar
  46. 46.
    Qureshi, N., J.P. Honovich, H. Hara, R.J. Cotter, and K. Takayama. 1988. Location of fatty acids in lipid A obtained from lipopolysaccharide of Rhodopseudomonas sphaeroides ATCC 17023. J. Biol. Chem. 263:5502–5504.PubMedGoogle Scholar
  47. 47.
    Qureshi, N., K. Takayama, D. Heller, and C. Fenselau. 1983. Position of ester groups in the lipid A backbone of lipopolysaccharides obtained from Salmonella typhimurium. J. Biol. Chem. 258:12947–12951.PubMedGoogle Scholar
  48. 48.
    Qureshi, N., K. Takayama, and E. Ribi. 1982. Purification and structural determination of non-toxic lipid A obtained from lipopolysaccharide of Salmonella typhimurium. J. Biol. Chem. 257:11808–11815.PubMedGoogle Scholar
  49. 49.
    Radika, K., and C.R. Raetz. 1988. Purification and properties of lipid A disaccharide synthase of Escherichia coli. J. Biol. Chem. 263:14859–14867.PubMedGoogle Scholar
  50. 50.
    Raetz, C.R.H. 1986. Molecular genetics of membrane phospholipid synthesis. Ann. Rev. Genet. 20:253–295.PubMedCrossRefGoogle Scholar
  51. 51.
    Raetz, C.R.H. 1987. Structure and biosynthesis of lipid A in Escherichia coli p. 498–503. In F.C. Neidhardt (ed.) Escherichia coli and Salmonella typhimurium cellular and molecular biology, vol. 1. American Society for Microbiology, Washington, D.C.Google Scholar
  52. 52.
    Raetz, C.R.H., and J. Foulds. 1977. Envelope composition and antibiotic hypersensitivity of Escherichia coli mutants defective in phosphatidylserine synthetase. J. Biol. Chem. 252:5911–5915.PubMedGoogle Scholar
  53. 53.
    Raetz, C.R.H., S. Purcell, M.V. Meyer, N. Qureshi, and K. Takayama. 1985. Isolation and characterization of eight lipid A precursors from a 3-deoxy-D-mannooctulosonic acid-deficient mutant of Salmonella typhimurium. J. Biol. Chem. 260:16080–16088.PubMedGoogle Scholar
  54. 54.
    Ray, B.L., G. Painter, and C.R.H. Raetz. 1984. The biosynthesis of gram-negative endotoxin: formation of lipid A disaccharides from monosaccharide precursors in extracts of Escherichia coli. J. Biol. Chem. 259:4852–4859.PubMedGoogle Scholar
  55. 55.
    B.L. Ray, and C.R.H. Raetz. 1987. The biosynthesis of gram-negative endotoxin: A novel kinase in Escherichia coli membranes that incorporates the 4’-phosphate of lipid A.J. Biol. Chem. 262:1122–1128.PubMedGoogle Scholar
  56. 56.
    Rich, P.D., L.W. Fung, C. Ho, and M.J. Osborn. 1977. Lipid A mutants of Salmonella typhimurium. Purification and characterization of a lipid A precursor produced by a mutant in 3-deoxy-n-mannooctulosonate-8-phosphate synthetase. J. Biol. Chem. 252:4904–4912.Google Scholar
  57. 57.
    Rick, P.D., and M.J. Osborn. 1977. Lipid A mutants of Salmonella typhimurium. Characterization of a conditional lethal mutant in 3-deoxy-D-mannooctulosonate-8phosphate synthetase. J. Biol. Chem. 252:4895–4903.PubMedGoogle Scholar
  58. 58.
    Rick, P.D., and D.A. Young. 1982. Relationship between cell death and altered lipid A synthesis in a temperature-sensitive lethal mutant of Salmonella typhimurium that is conditionally defective in 3-deoxy-n-manno-octulosonate-8-phosphate synthesis. J. Bacteriol. 150:456–464.PubMedGoogle Scholar
  59. 59.
    Rietschel, E.T. 1984. Handbook of endotoxin, vol 1: Chemistry of endotoxin, p. 1256. Elsevier Biomedical Press, Amsterdam.Google Scholar
  60. 60.
    Rietschel, E.T., H.W. Wollenweber, U. Zähringer, and O. Luderitz. 1982. Lipid A, the lipid component of bacterial lipopolysaccharides: relation of chemical structure to biological activity. Klin. Wochenschr. 60:705–709.PubMedCrossRefGoogle Scholar
  61. 61.
    Roppel, J., H. Mayer, and J. Weckesser. 1975. Identification of a 2,3-diamino-2,3dideoxyhexose in the lipid A component of lipopolysaccharides of Rhodopseudomonas viridis and Rhodopseudomonas palustris. Carbohydr. Res. 40:31–40.PubMedCrossRefGoogle Scholar
  62. 62.
    Strain, S.M., I.M. Armitage, L. Anderson, K. Takayama, N. Qureshi, and C.R.H. Raetz. 1985. Location of polar substituents and fatty acyl chains on lipid A precursors from a KDO-deficient mutant of Salmonella typhimurium: studies by1H13C, and31P nuclear magnetic resonance. J. Biol. Chem. 260:16089–16098.PubMedGoogle Scholar
  63. 63.
    Takayama, K., N. Qureshi, K. Hyver, J. Honovich, R.J. Cotter, P. Mascagni, and H. Schneider. 1986. Characterization of a structural series of lipid A obtained from the lipopolysaccharides of Neisseria gonorrhoeae. Combined laser desorption and fast atom bombardment mass spectral analysis of high performance liquid chromatography-purified dimethyl derivatives. J. Biol. Chem. 261:10624–10631.PubMedGoogle Scholar
  64. 64.
    Takayama, K., N. Qureshi, and P. Mascagni. 1983. Complete structure of lipid A obtained from the lipopolysaccharides of the heptoseless mutant of Salmonella typhimurium. J. Biol. Chem. 258:12801–12803.PubMedGoogle Scholar
  65. 65.
    Takayama, K., N. Qureshi, P. Mascagni, M.A. Nashed, and L. Anderson. 1983. Fatty acyl derivatives of glucosamine 1-phosphate in Escherichia coli and their relation to lipid A. Complete structure of a diacyl G1cN-1-P found in a phosphatidylglyceroldeficient mutant. J. Biol. Chem. 258:7379–7385.PubMedGoogle Scholar
  66. 66.
    Tamaki, S., T. Sato, and M. Matsuhashi. 1971. Role of lipopolysaccharides in antibiotic resistance and bacteriophase adsorption of Escherichia coli K-12. J. Bacteriol. 105:968–975.PubMedGoogle Scholar
  67. 67.
    Tomasiewicz, H.G., and C.S. McHenry. 1987. Sequence analysis of the Escherichia coli dnaE gene. J. Bacteriol. 169:5735–5744.PubMedGoogle Scholar
  68. 68.
    Vogler, A.P., S. Trentmann, and J.W. Lengeler. 1989. Alternative route for biosynthesis of amino sugars in Escherichia coli K-12 mutants by means of a catabolic isomerase. J. Bacteriol. 171:6586–6592.PubMedGoogle Scholar
  69. 69.
    Weckesser, J., and H. Mayer. 1988. Different lipid A types in lipopolysaccharides of phototrophic and related non-phototrophic bacteria. FEMS. Microbiol. Rev. 54:143–154.Google Scholar
  70. 70.
    Wollenweber, H.W., K.W. Broady, O. Luderitz, and E.T. Rietschel. 1982. The chemical structure of lipid A. Demonstration of amide-linked 3-acyloxyacyl residues in Salmonella minnesota Re lipopolysaccharide. Eur. J. Biochem. 124:191–198.PubMedCrossRefGoogle Scholar
  71. 71.
    Yasuzawa, T., M. Yoshida, M. Ichimura, K. Shirahata, and H. Sano. 1987. CV-1, a new antibiotic produced by a strain of Streptomyces sp;: II. Structure determination. J. Antibiotics 40:727–731.CrossRefGoogle Scholar
  72. 72.
    Young, L.S. 1985. Gram-negative sepsis, p. 454–474. In G.L. Mandell (ed.), Principles and practice of infectious diseases. John Wiley and Sons, New York.Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1992

Authors and Affiliations

  • Jack Coleman

There are no affiliations available

Personalised recommendations