1887

Abstract

The chemical structure and immunobiological activities of lipid A, an active centre of LPS, were investigated. LPS preparations of were extracted using a hot phenol/water method, after which purified lipid A specimens were prepared by weak acid hydrolysis, followed by normal phase and gel filtration chromatographic separation. The lipid A structure was determined by MS to be a diglucosamine backbone with diphosphates and five C normal chain acyl groups, including two acyloxyacyl groups at the 2 and 3 positions of the non-reducing side. lipid A and -type synthetic lipid A (compound 506) exhibited definite reactivity in amoebocyte lysate assays. The lethal toxicity of lipid A was nearly comparable to that of compound 506, and both induced nuclear factor-B activation in murine cells via Toll-like receptor (TLR)4/MD-2 but not TLR2, as well as various inflammatory cytokines in peritoneal macrophages of C3H/HeN mice but not C3H/HeJ mice. Furthermore, lipid A induced nearly the same amounts of tumour necrosis factor alpha, interleukin-6, and nitric oxide production by the murine alveolar macrophage cell line MH-S as compared with compound 506. These results indicate that possesses a penta-acylated lipid A, which is nearly identical to lipid A in regard to biological activities, while it also may be a crucial virulence factor of the bacterium.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.47327-0
2007-11-01
2020-07-09
Loading full text...

Full text loading...

/deliver/fulltext/jmm/56/11/1440.html?itemId=/content/journal/jmm/10.1099/jmm.0.47327-0&mimeType=html&fmt=ahah

References

  1. Adams G. A., Singh P. P. 1970; The chemical constitution of lipid A from Serratia marcescens . Can J Biochem 48:55–62
    [Google Scholar]
  2. Alexander C., Zähringer U. 2002; Chemical structure of lipid A – the primary immunomodulatory center of bacterial lipopolysaccharides. Trends Glycosci Glycotechnol 14:69–86 [CrossRef]
    [Google Scholar]
  3. Carbonell G. V., Della Colleta H. H., Yano T., Darini A. L., Levy C. E., Fonseca B. A. 2000; Clinical relevance and virulence factors of pigmented Serratia marcescens . FEMS Immunol Med Microbiol 28:143–149 [CrossRef]
    [Google Scholar]
  4. Carlon G. C., Dickinson P. C., Goldiner P. L., Turnbull A. D., Howland W. S. 1977; Serratia marcescens pneumonia. Arch Surg 112:1220–1224 [CrossRef]
    [Google Scholar]
  5. Coria-Jimenez R., Romero-Olvera J., Celis-Cruz C. 1998; Superficial hydrophobicity in Serratia marcescens strains of clinical origin. Res Microbiol 149:27–29 [CrossRef]
    [Google Scholar]
  6. Ernst R. K., Yi E. C., Guo L., Lim K. B., Burns J. L., Hackett M., Miller S. I. 1999; Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa . Science 286:1561–1565 [CrossRef]
    [Google Scholar]
  7. Flad H. D., Loppnow H., Rietschel E. T., Ulmer A. J. 1993; Agonists and antagonists for lipopolysaccharide-induced cytokines. Immunobiology 187:303–316 [CrossRef]
    [Google Scholar]
  8. Fuchs R. L., McPherson S. A., Drahos D. J. 1986; Cloning of a Serratia marcescens gene encoding chitinase. Appl Environ Microbiol 51:504–509
    [Google Scholar]
  9. Hejazi A., Falkiner F. R. 1997; Serratia marcescens . J Med Microbiol 46:903–912 [CrossRef]
    [Google Scholar]
  10. Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., Takeda K., Akira S. 1999; Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162:3749–3752
    [Google Scholar]
  11. Imoto M., Yoshimura N., Kusumoto S., Shiba T. 1984; Total synthesis of lipid A, active principle of bacterial endotoxin. Proc Jpn Acad Ser B 60:285–288 [CrossRef]
    [Google Scholar]
  12. Kärber G. 1931; Beitrag zür kollektiven behandlung pharmakologischer reihenversuche. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol 162:480–483 [CrossRef]
    [Google Scholar]
  13. Kato H., Haishima Y., Iida T., Tanaka A., Tanamoto K. 1998; Chemical structure of lipid A isolated from Flavobacterium meningosepticum lipopolysaccharide. J Bacteriol 180:3891–3899
    [Google Scholar]
  14. Kotani S., Takada H., Tsujimoto M., Ogawa T., Takahashi I., Ikeda T., Otsuka K., Shimauchi H., Kasai N. other authors 1985; Synthetic lipid A with endotoxic and related biological activities comparable to those of a natural lipid A from an Escherichia coli re-mutant. Infect Immun 49:225–237
    [Google Scholar]
  15. Kwitko A. O., Hamra L. K., Atkinson J. M. 1977; Serratia : opportunistic pathogen of increasing clinical importance. Med J Aust 2:119–121
    [Google Scholar]
  16. Luchi M., Morrison D. C. 2000; Comparable endotoxic properties of lipopolysaccharides are manifest in diverse clinical isolates of gram-negative bacteria. Infect Immun 68:1899–1904 [CrossRef]
    [Google Scholar]
  17. Makimura Y., Asai Y., Taiji Y., Sugiyama A., Tamai R., Ogawa T. 2006; Correlation between chemical structure and biological activities of Porphyromonas gingivalis synthetic lipopeptide derivatives. Clin Exp Immunol 146:159–168 [CrossRef]
    [Google Scholar]
  18. Maus U., Rosseau S., Knies U., Seeger W., Lohmeyer J. 1998; Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. Eur Respir J 11:534–541
    [Google Scholar]
  19. Mayeux P. R. 1997; Pathobiology of lipopolysaccharide. J Toxicol Environ Health 51:415–435 [CrossRef]
    [Google Scholar]
  20. Nagai Y., Akashi S., Nagafuku M., Ogata M., Iwakura Y., Akira S., Kitamura T., Kosugi A., Kimoto M., Miyake K. 2002; Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 3:667–672
    [Google Scholar]
  21. Nathan C. F. 1987; Secretory products of macrophages. J Clin Invest 79:319–326 [CrossRef]
    [Google Scholar]
  22. Ogawa T., Asai Y., Hashimoto M., Takeuchi O., Kurita T., Yoshikai Y., Miyake K., Akira S. 2002; Cell activation by Porphyromonas gingivalis lipid A molecule through Toll-like receptor 4- and myeloid differentiation factor 88-dependent signaling pathway. Int Immunol 14:1325–1332 [CrossRef]
    [Google Scholar]
  23. Pendino K. J., Laskin J. D., Shuler R. L., Punjabi C. J., Laskin D. L. 1993; Enhanced production of nitric oxide by rat alveolar macrophages after inhalation of a pulmonary irritant is associated with increased expression of nitric oxide synthase. J Immunol 151:7196–7205
    [Google Scholar]
  24. Poltorak A., He X., Smirnova I., Liu M. Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M. other authors 1998; Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088 [CrossRef]
    [Google Scholar]
  25. Raetz C. R. 1990; Biochemistry of endotoxins. Annu Rev Biochem 59:129–170 [CrossRef]
    [Google Scholar]
  26. Reid G., Sobel J. D. 1987; Bacterial adherence in the pathogenesis of urinary tract infection: a review. Rev Infect Dis 9:470–487 [CrossRef]
    [Google Scholar]
  27. Sanders C. V. Jr, Luby J. P., Johanson W. G. Jr, Barnett J. A., Sanford J. P. 1970; Serratia marcescens infections from inhalation therapy medications: nosocomial outbreak. Ann Intern Med 73:15–21 [CrossRef]
    [Google Scholar]
  28. Takayama K., Qureshi N., Mascagni P., Anderson L., Raetz C. R. 1983; Glucosamine-derived phospholipids in Escherichia coli . Structure and chemical modification of a triacyl glucosamine 1-phosphate found in a phosphatidylglycerol-deficient mutant. J Biol Chem 258:14245–14252
    [Google Scholar]
  29. Tanamoto K., Kato H., Haishima Y., Azumi S. 2001; Biological properties of lipid A isolated from Flavobacterium meningosepticum . Clin Diagn Lab Immunol 8:522–527
    [Google Scholar]
  30. Thomson N. R., Crow M. A., McGowan S. J., Cox A., Salmond G. P. 2000; Biosynthesis of carbapenem antibiotic and prodigiosin pigment in Serratia is under quorum sensing control. Mol Microbiol 36:539–556
    [Google Scholar]
  31. Traub W. H., Spohr M., Bauer D. 1987; Active immunization of NMRI mice against Serratia marcescens . I. Phenol-water lipopolysaccharide fractions and purified metalloproteases. Zentralbl Bakteriol Mikrobiol Hyg [A] 265:182–196
    [Google Scholar]
  32. Weinberg J. B., Granger D. L., Pisetsky D. S., Seldin M. F., Misukonis M. A., Mason S. N., Pippen A. M., Ruiz P., Wood E. R., Gilkeson G. S. 1994; The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease: increased nitric oxide production and nitric oxide synthase expression in MRL- lpr / lpr mice, and reduction of spontaneous glomerulonephritis and arthritis by orally administered NG-monomethyl-l-arginine. J Exp Med 179:651–660 [CrossRef]
    [Google Scholar]
  33. Westphal O., Jann K. 1965; Bacterial lipopolysaccharides. Extraction with phenol-water and further applications of the procedures. Methods Carbohydr Chem 5:83–91
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.47327-0
Loading
/content/journal/jmm/10.1099/jmm.0.47327-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error