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Structural basis for oligosaccharide-mediated adhesion of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients

Nature Structural Biology volume 9, pages 918–921 (2002)Cite this article

Abstract

Pseudomonas aeruginosa galactose- and fucose-binding lectins (PA-IL and PA-IIL) contribute to the virulence of this pathogenic bacterium, which is a major cause of morbidity and mortality in cystic fibrosis patients. The crystal structure of PA-IIL in complex with fucose reveals a tetrameric structure. Each monomer displays a nine-stranded, antiparallel b-sandwich arrangement and contains two close calcium cations that mediate the binding of fucose in a recognition mode unique among carbohydrate–protein interactions. Experimental binding studies, together with theoretical docking of fucose-containing oligosaccharides, are consistent with the assumption that antigens of the Lewis a (Lea) series may be the preferred ligands of this lectin. Precise knowledge of the lectin-binding site should allow a better design of new antibacterial-adhesion prophylactics.

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Figure 1: Structure of the PA-IIL–fucose complex.
Figure 2: Interactions of PA-IIL with calcium ions and fucose.
Figure 3: Molecular models of the docked oligosaccharides in the binding site of PA-IIL.

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Acknowledgements

We thank J. Lescar for his help in data collection and ESRF for provision of synchrotron facilities. C.H. is supported by a grant from the French association ANRS, M.W. is supported by the French minister program for invited scientists and partial financial support is acknowledged from the Ministry of Education of the Czech Republic.

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Authors and Affiliations

  1. E.S.R.F. Experiments Division, BP 220, Grenoble, F-38043, cedex, France

    Edward Mitchell

  2. CERMAV-CNRS (affiliated with Université Joseph Fourier), BP 53, Grenoble, F-38041, Cedex 09, France

    Corinne Houles, Michaela Wimmerova, Catherine Gautier, Serge Pérez & Anne Imberty

  3. Bar-Ilan University, Faculty of Life Sciences, Ramat Gan, 52900, Israel

    Dvora Sudakevitz & Nechama Gilboa-Garber

  4. Institute of Molecular and Cellular Biology, College of Medicine, Chang-Gung University, Kwei-San, 333, Tao-yuan, Taiwan

    Albert M. Wu

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Correspondence to Anne Imberty.

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Mitchell, E., Houles, C., Sudakevitz, D. et al. Structural basis for oligosaccharide-mediated adhesion of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Nat Struct Mol Biol 9, 918–921 (2002). https://doi.org/10.1038/nsb865

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