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

Stéphanie Perret, Charles Sabin, Claire Dumon, Martina Pokorná, Catherine Gautier, Oxana Galanina, Shahov Ilia, Nicolai Bovin, Magali Nicaise, Michel Desmadril, Nechama Gilboa-Garber, Michaela Wimmerová, Edward P. Mitchell, Anne Imberty

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100 Scopus citations


One of the mechanisms contributing to the protection by breastfeeding 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 × glucose analogue) bind to the lectin with dissociation constants of 2.2 × 10 -7 M and 3.6 × 10-7 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.

Original languageEnglish
Pages (from-to)325-332
Number of pages8
JournalBiochemical Journal
Issue number2
StatePublished - 15 Jul 2005


  • Crystal structure
  • Fucose
  • Human milk oligosaccharide
  • Lectin
  • Pseudomonas aeruginosa
  • Thermodynamics


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