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A LecA Ligand Identified from a Galactoside‐Conjugate Array Inhibits Host Cell Invasion by Pseudomonas aeruginosa
Author(s) -
Novoa Alexandre,
Eierhoff Thorsten,
Topin Jérémie,
Varrot Annabelle,
Barluenga Sofia,
Imberty Anne,
Römer Winfried,
Winssinger Nicolas
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201402831
Subject(s) - pseudomonas aeruginosa , glycoconjugate , ligand (biochemistry) , microbiology and biotechnology , biology , conjugate , virulence factor , lectin , divalent , virulence , chemistry , bacteria , biochemistry , receptor , genetics , mathematics , organic chemistry , gene , mathematical analysis
Abstract Lectin LecA is a virulence factor of Pseudomonas aeruginosa involved in lung injury, mortality, and cellular invasion. Ligands competing with human glycoconjugates for LecA binding are thus promising candidates to counteract P. aeruginosa infections. We have identified a novel divalent ligand from a focused galactoside(Gal)‐conjugate array which binds to LecA with very high affinity ( K d =82 n M ). Crystal structures of LecA complexed with the ligand together with modeling studies confirmed its ability to chelate two binding sites of LecA. The ligand lowers cellular invasiveness of P. aeruginosa up to 90 % when applied in the range of 0.05–5 μ M . Hence, this ligand might lead to the development of drugs against P. aeruginosa infection.