Structural basis for the interaction between human milk oligosaccharides and the bacterial lectin PA-IIL of Pseudomonas aeruginosa

• Published in: Biochemical journal Vol. 389; no. Pt 2; pp. 325 - 332
• Main Authors: Perret, Stéphanie, Sabin, Charles, Dumon, Claire, Pokorná, Martina, Gautier, Catherine, Galanina, Oxana, Ilia, Shahov, Bovin, Nicolai, Nicaise, Magali, Desmadril, Michel, Gilboa-Garber, Nechama, Wimmerová, Michaela, Mitchell, Edward P, Imberty, Anne
• Format: Journal Article
• Language: English
• Published: England Portland Press 15-07-2005; Portland Press Ltd
• Subjects: Adhesins, Bacterial - metabolism; Bacteria; Binding Sites; Carbohydrate Conformation; Carbohydrate Sequence; Crystallography; Humans; Lectins - metabolism; Milk, Human - chemistry; Models, Molecular; Molecular Sequence Data; Oligosaccharides - chemistry; Oligosaccharides - metabolism; Protein Binding; Protein Conformation; Pseudomonas aeruginosa; Pseudomonas aeruginosa - chemistry; Pseudomonas aeruginosa - metabolism; Substrate Specificity; Thermodynamics
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj20050079

One of the mechanisms contributing to the protection by breast-feeding of the newborn against enteric diseases is related to the ability of human milk oligosaccharides to prevent the attachment of pathogenic bacteria to the duodenual epithelium. Indeed, a variety of fucosylated oligosaccharides, specific to human milk, form part of the innate immune system. In the present study, we demonstrate the specific blocking of PA-IIL, a fucose-binding lectin of the human pathogen Pseudomonas aeruginosa, by milk oligosaccharides. Two fucosylated epitopes, Lewis a and 3-fucosyl-lactose (Lewis x glucose analogue) bind to the lectin with dissociation constants of 2.2x10(-7) M and 3.6x10(-7) M respectively. Thermodynamic studies indicate that these interactions are dominated by enthalpy. The entropy contribution is slightly favourable when binding to fucose and to the highest-affinity ligand, Lewis a. The high-resolution X-ray structures of two complexes of PA-IIL with milk oligosaccharides allow the precise determination of the conformation of a trisaccharide and a pentasaccharide. The different types of interaction between the oligosaccharides and the protein involve not only hydrogen bonding, but also calcium- and water-bridged contacts, allowing a rationalization of the thermodynamic data. This study provides important structural information about compounds that could be of general application in new therapeutic strategies against bacterial infections.