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. 1993 Oct;92(4):1875–1880. doi: 10.1172/JCI116779

Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells.

L Saiman 1, A Prince 1
PMCID: PMC288352  PMID: 8104958

Abstract

The basis for the unique association of Pseudomonas aeruginosa and the cystic fibrosis (CF) lung has remained obscure despite major advances in the understanding of the molecular genetic cause of this disease. There is evidence to suggest that abnormalities in CF transmembrane conductance regulator function result in alterations in the glycosylation of epithelial components. The number of asialoGM1 residues, as representative of a class of glycolipids which contain a GalNAc beta 1-4Gal sequence for P. aeruginosa attachment, was quantified by flow cytometric studies of respiratory epithelial cells in primary culture from both CF patients and normal subjects. Superficial asialoGM1 was detected on 12% of the CF cells as compared with 2.9% of the cells from normal control subjects (P = 0.03, chi 2 = 4.73), and more asialoGM1 residues were exposed on CF cells after modification by P. aeruginosa exoproducts. AsialoGM1, but not the sialylated glycolipid GM1, was demonstrated to be a receptor for 125I-labeled P. aeruginosa pilin, a major adhesin for this organism, and exogenous asialoGM1 was found to competitively inhibit P. aeruginosa adherence to epithelial cells, thus, confirming the biological role of the asialoGM1 receptor. Quantitative and qualitative differences in the sialylation of superficial glycolipids in CF epithelial cells may directly contribute to the colonization of the CF lung by P. aeruginosa.

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Selected References

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  1. Baker N., Hansson G. C., Leffler H., Riise G., Svanborg-Edén C. Glycosphingolipid receptors for Pseudomonas aeruginosa. Infect Immun. 1990 Jul;58(7):2361–2366. doi: 10.1128/iai.58.7.2361-2366.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barasch J., Kiss B., Prince A., Saiman L., Gruenert D., al-Awqati Q. Defective acidification of intracellular organelles in cystic fibrosis. Nature. 1991 Jul 4;352(6330):70–73. doi: 10.1038/352070a0. [DOI] [PubMed] [Google Scholar]
  3. Beachey E. H. Bacterial adherence: adhesin-receptor interactions mediating the attachment of bacteria to mucosal surface. J Infect Dis. 1981 Mar;143(3):325–345. doi: 10.1093/infdis/143.3.325. [DOI] [PubMed] [Google Scholar]
  4. CHERNICK W. S., BARBERO G. J. Studies on human tracheobronchial and submaxillary secretions in normal and pathophysiological conditions. Ann N Y Acad Sci. 1963 Mar 30;106:698–708. doi: 10.1111/j.1749-6632.1963.tb16678.x. [DOI] [PubMed] [Google Scholar]
  5. Cacalano G., Kays M., Saiman L., Prince A. Production of the Pseudomonas aeruginosa neuraminidase is increased under hyperosmolar conditions and is regulated by genes involved in alginate expression. J Clin Invest. 1992 Jun;89(6):1866–1874. doi: 10.1172/JCI115791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng P. W., Boat T. F., Cranfill K., Yankaskas J. R., Boucher R. C. Increased sulfation of glycoconjugates by cultured nasal epithelial cells from patients with cystic fibrosis. J Clin Invest. 1989 Jul;84(1):68–72. doi: 10.1172/JCI114171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Doig P., Todd T., Sastry P. A., Lee K. K., Hodges R. S., Paranchych W., Irvin R. T. Role of pili in adhesion of Pseudomonas aeruginosa to human respiratory epithelial cells. Infect Immun. 1988 Jun;56(6):1641–1646. doi: 10.1128/iai.56.6.1641-1646.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fukuta S., Magnani J. L., Twiddy E. M., Holmes R. K., Ginsburg V. Comparison of the carbohydrate-binding specificities of cholera toxin and Escherichia coli heat-labile enterotoxins LTh-I, LT-IIa, and LT-IIb. Infect Immun. 1988 Jul;56(7):1748–1753. doi: 10.1128/iai.56.7.1748-1753.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Govan J. R., Harris G. S. Pseudomonas aeruginosa and cystic fibrosis: unusual bacterial adaptation and pathogenesis. Microbiol Sci. 1986 Oct;3(10):302–308. [PubMed] [Google Scholar]
  10. Gruenert D. C., Basbaum C. B., Welsh M. J., Li M., Finkbeiner W. E., Nadel J. A. Characterization of human tracheal epithelial cells transformed by an origin-defective simian virus 40. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5951–5955. doi: 10.1073/pnas.85.16.5951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Irvin R. T., Doig P., Lee K. K., Sastry P. A., Paranchych W., Todd T., Hodges R. S. Characterization of the Pseudomonas aeruginosa pilus adhesin: confirmation that the pilin structural protein subunit contains a human epithelial cell-binding domain. Infect Immun. 1989 Dec;57(12):3720–3726. doi: 10.1128/iai.57.12.3720-3726.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Krivan H. C., Ginsburg V., Roberts D. D. Pseudomonas aeruginosa and Pseudomonas cepacia isolated from cystic fibrosis patients bind specifically to gangliotetraosylceramide (asialo GM1) and gangliotriaosylceramide (asialo GM2). Arch Biochem Biophys. 1988 Jan;260(1):493–496. doi: 10.1016/0003-9861(88)90473-0. [DOI] [PubMed] [Google Scholar]
  13. Krivan H. C., Roberts D. D., Ginsburg V. Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAc beta 1-4Gal found in some glycolipids. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6157–6161. doi: 10.1073/pnas.85.16.6157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lamb D., Reid L. The tracheobronchial submucosal glands in cystic fibrosis: a qualitative and quantitative histochemical study. Br J Dis Chest. 1972 Oct;66(4):239–247. doi: 10.1016/0007-0971(72)90042-3. [DOI] [PubMed] [Google Scholar]
  15. Ludwig D. S., Holmes R. K., Schoolnik G. K. Chemical and immunochemical studies on the receptor binding domain of cholera toxin B subunit. J Biol Chem. 1985 Oct 15;260(23):12528–12534. [PubMed] [Google Scholar]
  16. Lukacs G. L., Chang X. B., Kartner N., Rotstein O. D., Riordan J. R., Grinstein S. The cystic fibrosis transmembrane regulator is present and functional in endosomes. Role as a determinant of endosomal pH. J Biol Chem. 1992 Jul 25;267(21):14568–14572. [PubMed] [Google Scholar]
  17. Markwell M. A. A new solid-state reagent to iodinate proteins. I. Conditions for the efficient labeling of antiserum. Anal Biochem. 1982 Sep 15;125(2):427–432. doi: 10.1016/0003-2697(82)90025-2. [DOI] [PubMed] [Google Scholar]
  18. Ramphal R., Koo L., Ishimoto K. S., Totten P. A., Lara J. C., Lory S. Adhesion of Pseudomonas aeruginosa pilin-deficient mutants to mucin. Infect Immun. 1991 Apr;59(4):1307–1311. doi: 10.1128/iai.59.4.1307-1311.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ramphal R., Pyle M. Evidence for mucins and sialic acid as receptors for Pseudomonas aeruginosa in the lower respiratory tract. Infect Immun. 1983 Jul;41(1):339–344. doi: 10.1128/iai.41.1.339-344.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ramphal R., Sadoff J. C., Pyle M., Silipigni J. D. Role of pili in the adherence of Pseudomonas aeruginosa to injured tracheal epithelium. Infect Immun. 1984 Apr;44(1):38–40. doi: 10.1128/iai.44.1.38-40.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Reddy M. S. Human tracheobronchial mucin: purification and binding to Pseudomonas aeruginosa. Infect Immun. 1992 Apr;60(4):1530–1535. doi: 10.1128/iai.60.4.1530-1535.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  23. Saiman L., Cacalano G., Gruenert D., Prince A. Comparison of adherence of Pseudomonas aeruginosa to respiratory epithelial cells from cystic fibrosis patients and healthy subjects. Infect Immun. 1992 Jul;60(7):2808–2814. doi: 10.1128/iai.60.7.2808-2814.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Saiman L., Ishimoto K., Lory S., Prince A. The effect of piliation and exoproduct expression on the adherence of Pseudomonas aeruginosa to respiratory epithelial monolayers. J Infect Dis. 1990 Mar;161(3):541–548. doi: 10.1093/infdis/161.3.541. [DOI] [PubMed] [Google Scholar]
  25. Saito M., Sugano K., Nagai Y. Action of Arthrobacter ureafaciens sialidase on sialoglycolipid substrates. Mode of action and highly specific recognition of the oligosaccharide moiety of ganglioside GM1. J Biol Chem. 1979 Aug 25;254(16):7845–7854. [PubMed] [Google Scholar]
  26. Sajjan U., Reisman J., Doig P., Irvin R. T., Forstner G., Forstner J. Binding of nonmucoid Pseudomonas aeruginosa to normal human intestinal mucin and respiratory mucin from patients with cystic fibrosis. J Clin Invest. 1992 Feb;89(2):657–665. doi: 10.1172/JCI115632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Woods D. E., Straus D. C., Johanson W. G., Jr, Berry V. K., Bass J. A. Role of pili in adherence of Pseudomonas aeruginosa to mammalian buccal epithelial cells. Infect Immun. 1980 Sep;29(3):1146–1151. doi: 10.1128/iai.29.3.1146-1151.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yiu S. C., Lingwood C. A. Polyisobutylmethacrylate modifies glycolipid binding specificity of verotoxin 1 in thin-layer chromatogram overlay procedures. Anal Biochem. 1992 Apr;202(1):188–192. doi: 10.1016/0003-2697(92)90226-w. [DOI] [PubMed] [Google Scholar]

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