Towards Anti- Pseudomonas Aeruginosa Adhesion Therapy

  • Nechama Gilboa-Garber
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 408)


Pseudomonas aeruginosa infections may develop in immunocompromised patients in almost every tissue/organ, including: skin, eyes, ears, nasopharynx, bronchi and lungs, heart, kidneys and urinary tract, intestinal tract, liver, spleen, bones, brain and blood (bacteremia). They are the major cause of death in cystic fibrosis patients and endanger the life of patients suffering from extensive burns, chronic diseases and immunosuppressive ailments and treatments (e.g., for cancer repression or tissue transplantations). Their endurance is dependent on the tissue/host background. They are generally secondary to either immunodeficiency and primary infections or to metabolic abnormalities, which alter cell surface composition, exposing galactose- or N-acetylgalactosamine-bearing glycolipids. In primary infections preceding them, such as influenza, there is either removal of sialic acids or glycopeptides by the infecting factor sialidases or proteases. In metabolic abnormalities such as cystic fibrosis, the reason for the reduced glycolipid sialylation may be either sialylation deficiency (Imundo et al., 1995) or injurious sialo-/proteolysis caused by salivary or leukocytic enzymes.


Pseudomonas Aeruginosa Virulence Factor Sialic Acid Cystic Fibrosis Patient Alkaline Protease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Avichezer, D., and Gilboa-Gilboa, N., 1987, PA-II, the 1-fucose and d-mannose binding lectin of Pseudomonas aeruginosa stimulates peripheral lymphocytes and murine splenocytes, FEBS Lett 216:62–66.PubMedCrossRefGoogle Scholar
  2. Avichezer, D., Gilboa-Garber, N., Mumcuoglu, M., and Slavin, S., 1989, Adoptive transfer of resistance to Pseudomonas aeruginosa infection by splenocytes and bone marrow cells from BALB/c mice immunized by Pseudomonas aeruginosa lectin preparations, Infection 17:407–410.PubMedCrossRefGoogle Scholar
  3. Avichezer, D., and Gilboa-Garber, N., 1991, Anti-tumoral effects of Pseudomonas aeruginosa lectins on Lewis lung carcinoma cells cultured in vitro without and with murine splenocytes, Toxicon 29:1305–1313.PubMedCrossRefGoogle Scholar
  4. Avichezer, D., Katcoff, D. J., Garber, N. C., and Gilboa-Garber, N., 1992, Analysis of the amino acid sequence of the Pseudomonas aeruginosa galactophilic PA-I lectin, J. Biol Chem. 267:23023–23027.PubMedGoogle Scholar
  5. Avichezer, D., and Gilboa-Garber, N., 1995, Effects of Pseudomonas aeruginosa lectins on human ovarian, breast and oral epidermoid carcinoma cells, Proc. 1st FISEB Meeting, Eilat (Israel), p. 192.Google Scholar
  6. Bainton, N. J., Bycroft, B. W., Chhabra, S. R., Stead, P., Gledhill, L., Hill, P. J., Rees, C. E. D., Winson, M. K., Salmond, G. P. C., Stewart, G. S. A. B., and Williams, P., 1992, A general role for the lux autoinducer in bacterial cell signalling: control of antibiotic synthesis in Erwinia, Gene 116:87–91.PubMedCrossRefGoogle Scholar
  7. Baker, N. R., and Svanborg-Eden, C., 1989, Role of alginate in the adherence of Pseudomonas aeruginosa, in: Pseudomonas aeruginosa Infection (N. Hoiby, S. S. Pedersen, G. H. Sland et al., eds.), Karger AG, Basel, pp. 72–79.Google Scholar
  8. Bajolet-Laudinat, O., Girod-de Bentzmann, S., and Tournier, J. M., 1994, Cytotoxicity of Pseudomonas aeruginosa internal lectin PA-I to respiratory epithelial cells in primary culture, Infect. Immun. 62:4481–4487.PubMedGoogle Scholar
  9. Brint, M; and Ohman, D. E., 1995, Synthesis of multiple exoproducts in Pseudomonas aeruginosa in the control of Rh1R-Rh1l, another set of regulators in strain PAO1 with homology to the auto-inducer responsive LuxR-LuxI family. J. Bacteriol. 177: 7155–7163.PubMedGoogle Scholar
  10. Camara, M., Winson, M. K., Latifi, A., Falconer, C., Briggs, G. S., Chhabra, S. R., Foglino, M., Garber, N. C., Gilboa-Garber, N., Belz, A., Bycroft, B. W., Lazdunski, A., Stewart, G. S. A. B., and Williams, P., 1995, Multiple quorum sensing modulons interactively regulate production of virulence determinants and secondary metabolites in Pseudomonas aeruginosa, Proc. “Pseudomonas 1995” 5th Int. Symp. on Pseudomonas Biotechnol. and Mol. Biol., Tsukuba, Japan, p. 159.Google Scholar
  11. Ceri, H., McArthur, H. A. I., and Whitfield, C., 1986, Association of alginate from Pseudomonas aeruginosa with two forms of heparin-binding lectin isolated from rat lung, Infect. Immun. 51:1–5.PubMedGoogle Scholar
  12. DiMango, E., Zar, H. J., Bryan, R., and Prince, A., 1995, Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8, J. Clin. Invest. 96:2204–2210.CrossRefGoogle Scholar
  13. Eberhard, A., Burlingame, A. L., Eberhard, C., Kenyon, G. L., Nealson, K. H., and Oppenheimer, N. J., 1981, Structural identification of autoinducer of Photobacterium fischeri luciferase, Biochemistry 20:2444–2449.PubMedCrossRefGoogle Scholar
  14. Fujii, T., Kadota, J., Kawakami, K., Iida, K., Shirai, R., Kaseda, M., Kawamoto, S., and Kohno, S., 1995, Long term effect of erythromycin therapy in patients with chronic Pseudomonas aeruginosa infection, Thorax 50:1246–1252.PubMedCrossRefGoogle Scholar
  15. Gambello, M. J., and Iglewski, B. H., 1991, Cloning and characterization of the Pseudomonas aeruginosa las R gene, a transcriptional activator of elastase expression, J. Bacteriol. 173:3000–3009.PubMedGoogle Scholar
  16. Gambello, M. J., Kaye, S., and Iglewski, B. H., 1993, Las R of Pseudomonas aeruginosa is a transcriptional activator of the alkaline protease gene (apr) and an enhancer of exotoxin A expression, Infect. Immun. 61:1180–1184.PubMedGoogle Scholar
  17. Garber, N., Sharon, N., Shohet, D., Lam, J. S., and Doyle, R. J., 1985, Contribution of hydrophobicity to the hemagglutination reactions of Pseudomonas aeruginosa, Infect. Immun. 50:336–337.PubMedGoogle Scholar
  18. Garber, N., Guempel, U., Gilboa-Garber, N., and Doyle, R. J., 1987, Specificity of fucose-binding lectin of Pseudomonas aeruginosa, FEMS Microbiol Lett. 48:331–334.CrossRefGoogle Scholar
  19. Garber, N., Guempel, U., Belz, A., Gilboa-Garber, N., and Doyle, R. J., 1992, On the specificity of the d-galactose-binding lectin (PA-I) of Pseudomonas aeruginosa and its strong binding to hydrophobic derivatives of d-galactose and thiogalactose, Biochim. Biophys. Acta 1116:331–333.PubMedGoogle Scholar
  20. Garber, N. C., Hammer-Müntz, O., Belz, A., and Krakower, Y., 1995, The lux autoinducer stimulates the production of the lectins of Pseudomonas aeruginosa, ISM Lett. 15:164.Google Scholar
  21. Gilboa-Garber, N., 1972, Inhibition of broad spectrum hemagglutinin from Pseudomonas aeruginosa by d-galactose and its derivatives, FEBS Lett. 20:242–244.PubMedCrossRefGoogle Scholar
  22. Gilboa-Garber, N., 1982, Pseudomonas aeruginosa lectins, in: Methods in Enzymology, Vol. 83, “Complex Carbohydrates, Part D”, [Colowick and Kaplan (Ginsburg), eds.], Academic Press, Inc., New York, pp. 378–385.Google Scholar
  23. Gilboa-Garber, N., 1986, Lectins of Pseudomonas aeruginosa: properties, biological effects and applications, in: Microbial Lectin and Agglutinins: Properties and Biological Activity (D. Mirelman, ed.), John Wiley & Sons, New York, pp. 255–269.Google Scholar
  24. Gilboa-Garber, N., and Blonder, E., 1979, Augmented osmotic hemolysis of human erythrocytes exposed to the galactosephilic lectin of Pseudomonas aeruginosa, Israel J. Med. Sci. 15:537–539.PubMedGoogle Scholar
  25. Gilboa-Garber, N., Buxenbaum, R., Mizrahi, L., and Avichezer, D., 1981, Correlation between lectins and protease activities in Pseudomonas aeruginosa, XI World Cong. Pathol., Jerusalem, Israel, p. 98.Google Scholar
  26. Gilboa-Garber, N., Mizrahi, L., Buxenbaum, R., and Sudakevitz, D., 1982, The Pseudomonas aeruginosa lectins are linked to the production of protease and other exocellular enzymes, Israel J. Med. Sci. 18:19.Google Scholar
  27. Gilboa-Garber, N., and Sudakevitz, D., 1982, The use of Pseudomonas aeruginosa lectin preparations as a vaccine, in: Advances in Pathology, Vol. 1 (E. Levy, ed.), Pergamon Press, Ltd., Oxford, pp. 31–33.Google Scholar
  28. Gilboa-Garber, N., and Mizrahi, L., 1985, Pseudomonas lectin PA-I detects hybrid product of blood group AB genes in saliva. Experientia 41:681–682.PubMedCrossRefGoogle Scholar
  29. Gilboa-Garber, N., and Garber, N., 1989, Microbial lectin cofunction with lytic activities as a model for a general basic lectin role, FEMS Microbiol Rev. 63:211–222.CrossRefGoogle Scholar
  30. Gilboa-Garber, N., Sudakevitz, D., Sheffi, M., Sela, R., and Levene, C., 1994, PA-I and PA-II lectin interactions with the ABO(H) and P blood group glycosphingolipid antigens may contribute to the broad spectrum adherence of Pseudomonas aeruginosa to human tissues in secondary infections, Glycoconjugate J. 11:414–417.CrossRefGoogle Scholar
  31. Glick, J., Malik, Z., and Garber, N., 1981, Lectin-bearing protoplasts of Pseudomonas aeruginosa induce capping in human peripheral blood lymphocytes, Microbios., 32:181–188.PubMedGoogle Scholar
  32. Grant, G., Bardocz, S., Ewen, S. W. B., Brown, D. S., Duguid, T. J., Pusztai, A., Avichezer, D., Sudakevitz, D., Belz, A., Garber, N. C., and Gilboa-Garber, N., 1995, Purified Pseudomonas aeruginosa PA-I lectin induces gut growth when orally ingested by rats, FEMS Immun. Med. Microbiol. 11:191–196.CrossRefGoogle Scholar
  33. Hammer-Münz, O., Krakower, Y., and Garber, N.C., 1996, N-(3-oxohexanoyl)-L-homoserine lactone increases both lectin production in Pseudomonas aeruginosa and its virulence to mice, ISM News 20:21.Google Scholar
  34. Hazlett, L. D., Moon, M., and Berk, R. S., 1986, In vivo identification of sialic acid as the ocular receptor of Pseudomonas aeruginosa, Infect. Immun. 51:687–689.PubMedGoogle Scholar
  35. Imundo, L., Barasch, J., Prince, A., and Al-Awqati, Q., 1995, Cystic fibrosis epithelial cells have a receptor for pathogenic bacteria on their apical surface, Proc. Natl Acad. Sci. USA 92:3019–3023.PubMedCrossRefGoogle Scholar
  36. Itoh, M., Hetterich, P., Isecke, R., Brossmer, R., and Klenk, H. -D., 1995, Suppression of influenza virus infection by an N-thioacetylneuraminic acid acrylamide copolymer resistant to neuraminidase, Virology 212:340–347.PubMedCrossRefGoogle Scholar
  37. Lanne, B., Ciopraga, J., Bergstrom, J., Motas, C., and Karlsson, K.-A., 1994, Binding of the galactose-specific Pseudomonas aeruginosa lectin, PA-I, to glycosphingolipids and other glycoconjugates, Glycoconjugate J. 11:292–298.CrossRefGoogle Scholar
  38. Latifi, A., Winson, M. K., Foglino, M., Bycroft, B. W., Stewart, S. A. B., Lazdunski, A., and Williams, P., 1995, Multiple homologues of Lux R and Lux I control expression of virulence determinants and secondary metabolites through quorum sensing in Pseudomonas aeruginosa PAO1, Mol. Microbiol. 17:333–343.PubMedCrossRefGoogle Scholar
  39. Liu, P. V., 1974, Extracellular toxins of Pseudomonas aeruginosa, J. Infect. Dis. 130(suppl.):94–99.CrossRefGoogle Scholar
  40. Kaplan, H. B., and Greenberg, E. P., 1987, Overproduction and purification of the lux R gene product: transcriptional activation of the Vibrio fischeri luminescence system. Proc. Natl Acad. Sci. USA 84:6639–6643.PubMedCrossRefGoogle Scholar
  41. Kita, E., Sawaki, M., Oku, D., Hamuro, A., Mikasa, K., Konishi, M., Emoto, M., Takeuchi, S., Narita, N., and Kashiba, S., 1991, Suppression of virulence factors of Pseudomonas aeruginosa by erythromycin, J. Antimicrob. Chemther. 27:273–284.CrossRefGoogle Scholar
  42. Krivan, H. C., Ginsburg, V., and Roberts, D. D., 1988, Pseudomonas aeruginosa and Pseudomonas cepacia isolated from cystic fibrosis patients bind specifically to gangliotetraosylceramide (asialo GM1) and gangliotriaosyl-ceramide (asialo GM2), Arch. Biochem. Biophys. 260:493–496.PubMedCrossRefGoogle Scholar
  43. Mammen, M., Dahmann, G., and Whitesides, G. M., 1995, Effective inhibitors of hemagglutination by influenza virus synthesized from polymers having active ester groups. Insight into mechanism of inhibition, J. Med. Chem. 38:4179–4190.PubMedCrossRefGoogle Scholar
  44. Meighen, E. A., 1991, Molecular biology of bacterial bioluminescence, Microbiol Rev. 55:123–142.PubMedGoogle Scholar
  45. Molinari, G., Guzman, C. A., Pesce, A., Schito, G. C., 1993, Inhibition of Pseudomonas aeruginosa virulence factors by subinhibitory concentrations of azithromycin and other macrolide antibiotics, J. Antimicrob. Chemother. 31:681–688.PubMedCrossRefGoogle Scholar
  46. Mühlradt, P.F., Tsai, H., and Conradt, P., 1986, Effects of pyocyanine, a blue pigment from Pseudomonas aeruginosa, on separate steps of T cell activation: interleukin 2 (IL2) production, IL2 receptor formation, proliferation and induction of cytolytic activity, Eur. J. Immunol. 16:434–440.PubMedCrossRefGoogle Scholar
  47. Muller, M., and Sorrell, T. C., 1991, Production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by human neutrophils is inhibited by Pseudomonas aeruginosa phenazine derivatives, Infect. Immun. 59:3316–3318.PubMedGoogle Scholar
  48. Nicas, T. I., and Iglewski, B. H., 1985, The contribution of exoproducts to virulence of Pseudomonas aeruginosa, Can. J. Microbiol. 31:387–392.PubMedCrossRefGoogle Scholar
  49. Passador, L., Cook, J. M., Gambello, M. J., Rust, L., and Iglewski, B. H., 1993, Expression of Pseudomonas aeruginosa virulence genes required cell-to-cell communication, Science 260:1127–1130.PubMedCrossRefGoogle Scholar
  50. Pearson, J. P., Gray, K. M., Passador, L., Tucker, K. D., Eberhard, J. P., Iglewski, B. H. and Greenberg, E. P., 1994, Structure of autoinducer required for expression of Pseudomonas aeruginosa virulence genes, Proc. Natl. Acad. Sci. USA 91:197–201.PubMedCrossRefGoogle Scholar
  51. Piatti, G., 1994, Bacterial adhesion to respiratory mucosa and its modulation by antibiotics at sub-inhibitory concentrations, Pharmacol. Res. 30:289–299.PubMedCrossRefGoogle Scholar
  52. Prince, A., 1992, Adhesins and receptors of Pseudomonas aeruginosa associated with infection of the respiratory tract, Microbiol. Pathog. 13:251–260.CrossRefGoogle Scholar
  53. Ramphai, R., andPyle, M., 1983, Evidence for mucins and sialic acid as receptors for Pseudomonas aeruginosa in the lower respiratory tract, Infect. Immun. 41:339–344.Google Scholar
  54. Ramphai, R., and Pier, G. B., 1985, Role of Pseudomonas aeruginosa mucoid exopolysaccharide in adherence to tracheal cells, Infect. Immun. 47:1–4.Google Scholar
  55. Sharabi, Y., and Gilboa-Garber, N., 1979, Mitogenic stimulation of human lymphocytes by Pseudomonas aeruginosa galactosephilic lectin, FEMS Microbiol. Lett. 5:273–276.CrossRefGoogle Scholar
  56. Sheth, H. B., Lee, K. K., Wong, W. Y., Srivastava, G., Hindsgaul, O., Leung, O., Krepinsky, G., Hodges, R.S., Paranchych, W., and Irvin, R.T., 1994, The pili of Pseudomonas aeruginosa strains PAK and PAO bind specifically to the carbohydrate sequence βGalNAc(l–4)βGal found in glycosphingolipids asialo-GM, and asialo-GM2, Mol. Microbiol. 11:715–723.PubMedCrossRefGoogle Scholar
  57. Shibl, A. M., and Al-Sowaygh, I. A., 1980, Antibiotic inhibition of protease production by Pseudomonas aeruginosa, J. Med. Microbiol. 13:345–349.PubMedCrossRefGoogle Scholar
  58. Sofer, D., and Gilboa-Garber, N., 1995, Effect of antibodies to Pseudomonas aeruginosa lectins in the presence of complement on the bacterium growth in vitro and its harm in vivo, Proc. 1st F.I.S.E.B. Meeting, Eilat, Israel, p. 134.Google Scholar
  59. Sofer, D., Gilboa-Garber, N. and Garber, N.C., 1996, Erythomycin, which does not affect Pseudomonas aeruginosa growth, blocks the corregulated production of virulence factors and lectins by inhibiting synthesis of corregulatory autoinducer molecules, Proc. 8th IUMS Congress of Bacteriol. and Applied Microbiol., Jerusalem, Israel.Google Scholar
  60. Sorensen, R.U., Klinger, J.D., Cash, H.A., Chase, P.A., and Dearborn, G.D., 1983, In vitro inhibition of lymphocyte proliferation by Pseudomonas aeruginosa phenazine pigments, Infect. Immun. 41:321–330.PubMedGoogle Scholar
  61. Steuer, M. K., Herbst, H., Beuth, J., Steuer, M., Pulverer, G., Matthias, R., 1993, Inhibition of lectin mediated bacterial adherence by receptor blocking carbohydrates in patients with Pseudomonas aeruginosa induced otitis externa: A prospective phase-II study, Otorhinolaryngol. Nova 3:19–25.CrossRefGoogle Scholar
  62. Sudakevitz, D., Gilboa-Garber, N., and Mizrahi, L., 1979, Regulation of lectin production in Pseudomonas aeruginosa by culture medium composition, Isr. J. Med. Sci. 15:97.Google Scholar
  63. Sudakevitz, D., and Gilboa-Garber, N., 1987, Immunization of mice against various strains of Pseudomonas aeruginosa by using Pseudomonas lectin vaccine, FEMS Microbiol. Lett. 43:313–315CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Nechama Gilboa-Garber
    • 1
  1. 1.Department of Life SciencesBar-Ilan UniversityRamat-GanIsrael

Personalised recommendations