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Conformations of cell surface oligosaccharides and recognition by lectins from pathogens
Author(s) -
Imberty Anne
Publication year - 2004
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.0959-9673.2004.0390d.x
Subject(s) - microbiology and biotechnology , pseudomonas aeruginosa , mucin , cystic fibrosis , virulence , epitope , glycoprotein , fucose , mucus , chemistry , biology , bacterial adhesin , glycosylation , lectin , bacteria , biochemistry , immunology , antigen , gene , genetics , ecology
Pseudomonas aeruginosa is essentially a saprophytic bacterium that can turn into an aggressive pathogen when in contact with damaged and inflamed tissues such as burns and lungs of cystic fibrosis (CF) patients. In all of these cases, the host cell surfaces present altered glycosylations. The most studied example is that of CF where point mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene, results in altered ion movements and also influences the N ‐glycosylation of the CFTR protein and other cell surface glycoproteins. Increased fucosylation and decreased sialylation with higher levels of Lewis x and Lewis a epitopes correlate to P. aeruginosa ‐specific binding. In addition, both the mucus covering the airway epithelia of CF patients and their salivary mucins display higher levels of sialylated and sulfated Lewis oligosaccharides that attract P. aeruginosa . The galactose‐ and fucose‐binding (PA‐IL and PA‐IIL) lectins of P. aeruginosa contribute to the virulence of this pathogenic bacterium, which is a major cause of morbidity and mortality in CF patients. Database searching in newly sequenced genomes indicates that the presence of these lectins is characteristics of high environmental adaptability of some opportunistic bacteria. The crystal structures of PA‐IL and PA‐IIL lectins have been solved in complex with the corresponding monosaccharides. Molecular modelling studies were used in order to predict the binding mode of PA‐IIL with complex oligosaccharides. Combination of theoretical studies with binding assays give clear indication that the histo‐blood group epitope Lewis a could be the biological ligand present in the lung of CF patients.