Skip to main content
SpringerLink
Log in

Inhibition of the bacterial lectins of Pseudomonas aeruginosa with monosaccharides and peptides

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Pseudomonas aeruginosa (PA) can cause infections in compromised hosts by interacting with the glycocalyx of host epithelial cells. It binds to glycostructures on mucosal surfaces via two lectins, which are carbohydrate-binding proteins, named PA-IL and PA-IIL, and blocking this interaction is, thus, an attractive anti-adhesive strategy. The aim of this study was to determine by ciliary beat frequency (CBF) analysis whether monosaccharides or peptides mimicking glycostructures represent blockers of PA lectin binding to human airway cilia. The treatment with monosaccharides and peptides alone did not change the CBF compared to controls and the tested compounds did not influence the cell morphology or survival, with the exception of peptide pOM3. PA-IL caused a decrease of the CBF within 24 h. D-galactose as well as the peptides mimicking HNK-1, polysialic acid and fucose compensated the CBF-modulating effect of PA-IL with different affinities. PA-IIL also bound to the human airway cilia in cell culture and resulted in a decrease of the CBF within 24 h. L(−)-fucose and pHNK-1 blocked the CBF-decreasing effect of PA-IIL. The HNK-1-specific glycomimetic peptide had a high affinity for binding to both PA-IL and PA-IIL, and inhibited the ciliotoxic effect of both lectins, thus, making it a strong candidate for a therapeutic anti-adhesive drug.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kirkeby S, Moe D (2005) Analyses of Pseudomonas aeruginosa lectin binding to alpha-galactosylated glycans. Curr Microbiol 50(6):309–313

    Article  PubMed  CAS  Google Scholar 

  2. Gang RK, Bang RL, Sanyal SC, Mokaddas E, Lari AR (1999) Pseudomonas aeruginosa septicaemia in burns. Burns 25(7):611–616

    Article  PubMed  CAS  Google Scholar 

  3. Garau J, Gomez L (2003) Pseudomonas aeruginosa pneumonia. Curr Opin Infect Dis 16(2):135–143

    Article  PubMed  CAS  Google Scholar 

  4. Gilboa-Garber N (1982) Pseudomonas aeruginosa lectins. Methods Enzymol 83:378–385

    Article  PubMed  CAS  Google Scholar 

  5. Adam EC, Mitchell BS, Schumacher DU, Grant G, Schumacher U (1997) Pseudomonas aeruginosa II lectin stops human ciliary beating: therapeutic implications of fucose. Am J Respir Crit Care Med 155(6):2102–2104

    PubMed  CAS  Google Scholar 

  6. Gilboa-Garber N, Garber N (1989) Microbial lectin cofunction with lytic activities as a model for a general basic lectin role. FEMS Microbiol Rev 5(3):211–221

    Article  PubMed  CAS  Google Scholar 

  7. Winzer K, Falconer C, Garber NC, Diggle SP, Camara M, Williams P (2000) The Pseudomonas aeruginosa lectins PA-IL and PA-IIL are controlled by quorum sensing and by RpoS. J Bacteriol 182(22):6401–6411

    Article  PubMed  CAS  Google Scholar 

  8. Zhang LH, Dong YH (2004) Quorum sensing and signal interference: diverse implications. Mol Microbiol 53(6):1563–1571

    Article  PubMed  CAS  Google Scholar 

  9. Hauber HP, Schulz M, Pforte A, Mack D, Zabel P, Schumacher U (2008) Inhalation with fucose and galactose for treatment of Pseudomonas aeruginosa in cystic fibrosis patients. Int J Med Sci 5(6):371–376

    PubMed  CAS  Google Scholar 

  10. Steuer MK, Herbst H, Beuth H, Beuth J, Steuer M, Pulverer G, Matthias R (1993) Hemmung der bakteriellen Adhäsion durch Lektinblockade bei durch Pseudomonas aeruginosa induzierter Otitis externa im Vergleich zur lokalen Therapie mit Antibiotika. Otorhinolaryngol Nova 3:19–25

    Article  Google Scholar 

  11. von Bismarck P, Schneppenheim R, Schumacher U (2001) Successful treatment of Pseudomonas aeruginosa respiratory tract infection with a sugar solution—a case report on a lectin based therapeutic principle. Klin Pädiatr 213(5):285–287

    Article  Google Scholar 

  12. Garber N, Guempel U, Belz A, Gilboa-Garber N, Doyle RJ (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(3):331–333

    Article  PubMed  CAS  Google Scholar 

  13. Haddadin RN, Saleh SA, Mahmoud RA, Shehabi AA (2010) Multiple drug resistance and strength of attachment to surfaces in Pseudomonas aeruginosa isolates. Lett Appl Microbiol 51(1):48–53

    PubMed  CAS  Google Scholar 

  14. Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O (2010) Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 35(4):322–332

    Article  PubMed  Google Scholar 

  15. Oldenburg KR, Loganathan D, Goldstein IJ, Schultz PG, Gallop MA (1992) Peptide ligands for a sugar-binding protein isolated from a random peptide library. Proc Natl Acad Sci USA 89(12):5393–5397

    Article  PubMed  CAS  Google Scholar 

  16. Scott JK, Loganathan D, Easley RB, Gong X, Goldstein IJ (1992) A family of concanavalin A-binding peptides from a hexapeptide epitope library. Proc Natl Acad Sci USA 89(12):5398–5402

    Article  PubMed  CAS  Google Scholar 

  17. Mewe M, Tielker D, Schönberg R, Schachner M, Jaeger KE, Schumacher U (2005) Pseudomonas aeruginosa lectins I and II and their interaction with human airway cilia. J Laryngol Otol 119(8):595–599

    Article  PubMed  Google Scholar 

  18. Wu L, Holbrook C, Zaborina O, Ploplys E, Rocha F, Pelham D, Chang E, Musch M, Alverdy J (2003) Pseudomonas aeruginosa expresses a lethal virulence determinant, the PA-I lectin/adhesin, in the intestinal tract of a stressed host: the role of epithelia cell contact and molecules of the Quorum Sensing Signaling System. Ann Surg 238(5):754–764

    Article  PubMed  Google Scholar 

  19. Chen CP, Song SC, Gilboa-Garber N, Chang KS, Wu AM (1998) Studies on the binding site of the galactose-specific agglutinin PA-IL from Pseudomonas aeruginosa. Glycobiology 8(1):7–16

    Article  PubMed  CAS  Google Scholar 

  20. Imberty A, Wimmerová M, Mitchell EP, Gilboa-Garber N (2004) Structures of the lectins from Pseudomonas aeruginosa: insight into the molecular basis for host glycan recognition. Microbes Infect 6(2):221–228

    Article  PubMed  CAS  Google Scholar 

  21. Johansson EMV, Kolomiets E, Rosenau F, Jaeger K-E, Darbre T, Reymond J-L (2007) Combinatorial variation of branching length and multivalency in a large (390 625 member) glycopeptide dendrimer library: ligands for fucose-specific lectins. New J Chem 31(7):1291–1299

    Article  CAS  Google Scholar 

  22. Kolomiets E, Johansson EMV, Renaudet O, Darbre T, Reymond J-L (2007) Neoglycopeptide dendrimer libraries as a source of lectin binding ligands. Org Lett 9(8):1465–1468

    Article  PubMed  CAS  Google Scholar 

  23. Sears P, Wong CH (1999) Carbohydrate mimetics: a new strategy for tackling the problem of carbohydrate-mediated biological recognition. Angew Chem Int Ed Engl 38(16):2300–2324

    Article  PubMed  Google Scholar 

  24. Bertozzi CR, Kiessling LL (2001) Chemical glycobiology. Science 291(5512):2357–2364

    Article  PubMed  CAS  Google Scholar 

  25. Kleene R, Schachner M (2004) Glycans and neural cell interactions. Nat Rev Neurosci 5(3):195–208

    Article  PubMed  CAS  Google Scholar 

  26. Di Benedetto G, Gill J, Lopez-Vidriero MT, Clarke SW (1989) The effect of cryopreservation on ciliary beat frequency of human respiratory epithelium. Cryobiology 26(4):328–332

    Article  PubMed  Google Scholar 

  27. Wulffraat NM, Veerman AJ, Stamhuis IH (1985) Frequency and coordination of ciliary beat after cryopreservation of respiratory epithelium. Cryobiology 22(2):105–110

    Article  PubMed  CAS  Google Scholar 

  28. Tielker D, Hacker S, Loris R, Strathmann M, Wingender J, Wilhelm S, Rosenau F, Jaeger KE (2005) Pseudomonas aeruginosa lectin LecB is located in the outer membrane and is involved in biofilm formation. Microbiology 151(Pt 5):1313–1323

    Article  PubMed  CAS  Google Scholar 

  29. Garber N, Guempel U, Gilboa-Garber N, Royle RJ (1987) Specificity of the fucose-binding lectin of Pseudomonas aeruginosa. FEMS Microbiol Lett 48(3):331–334

    Article  CAS  Google Scholar 

  30. Gilboa-Garber N, Katcoff DJ, Garber NC (2000) Identification and characterization of Pseudomonas aeruginosa PA-IIL lectin gene and protein compared to PA-IL. FEMS Immunol Med Microbiol 29(1):53–57

    Article  PubMed  CAS  Google Scholar 

  31. Lamblin G, Degroote S, Perini JM, Delmotte P, Scharfman A, Davril M, Lo-Guidice JM, Houdret N, Dumur V, Klein A, Rousse P (2001) Human airway mucin glycosylation: a combinatory of carbohydrate determinants which vary in cystic fibrosis. Glycoconj J 18(9):661–684

    Article  PubMed  CAS  Google Scholar 

  32. Kizuka Y, Matsui T, Takematsu H, Kozutsumi Y, Kawasaki T, Oka S (2006) Physical and functional association of glucuronyltransferases and sulfotransferase involved in HNK-1 biosynthesis. J Biol Chem 281(19):13644–13651

    Article  PubMed  CAS  Google Scholar 

  33. Eberhardt KA, Irintchev A, Al-Majed AA, Simova O, Brushart TM, Gordon T, Schachner M (2006) BDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor nerves and promotes functional recovery after peripheral nerve repair. Exp Neurol 198(2):500–510

    Article  PubMed  CAS  Google Scholar 

  34. Simova O, Irintchev A, Mehanna A, Liu J, Dihné M, Bächle D, Sewald N, Loers G, Schachner M (2006) Carbohydrate mimics promote functional recovery after peripheral nerve repair. Ann Neurol 60(4):430–437

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Märker, T. Cöllen and C. Knies for their excellent technical assistance. The authors are grateful to the Christiane Herzog Stiftung for providing the funds for the inverted microscope. Prof. Schachner thanks SFB470 for the financial support.

Author information

Authors and Affiliations

  1. Department of Anatomy II: Experimental Morphology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    H. Gustke, N. Nehmann & U. Schumacher

  2. Center for Molecular Neurobiology, University Hamburg, Falkenried 94, 20251, Hamburg, Germany

    R. Kleene, G. Loers & M. Schachner

  3. ENT Hospital, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    M. Jaehne

  4. Institute for Molecular Enzyme Technology, Heinrich-Heine-University Düsseldorf, Research Centre Juelich, 52426, Juelich, Germany

    K.-M. Bartels & K.-E. Jaeger

Authors
  1. H. Gustke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Kleene
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Loers
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Nehmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Jaehne
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K.-M. Bartels
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K.-E. Jaeger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Schachner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. U. Schumacher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U. Schumacher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gustke, H., Kleene, R., Loers, G. et al. Inhibition of the bacterial lectins of Pseudomonas aeruginosa with monosaccharides and peptides. Eur J Clin Microbiol Infect Dis 31, 207–215 (2012). https://doi.org/10.1007/s10096-011-1295-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-011-1295-x

Keywords

Search

Navigation