title: A LecA ligand identified from a galactoside-conjugate array inhibits host cell invasion by Pseudomonas aeruginosa.
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 (Kd = 82 nM). 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 μM. Hence, this ligand might lead to the development of drugs against P. aeruginosa infection.
authors.affiliation: Department of Organic Chemistry, University of Geneva (Switzerland).
authors.forename: Alexandre
authors.initials: A
authors.lastname: Novoa
authors.forename: Thorsten
authors.initials: T
authors.lastname: Eierhoff
authors.forename: Jérémie
authors.initials: J
authors.lastname: Topin
authors.forename: Annabelle
authors.initials: A
authors.lastname: Varrot
authors.forename: Sofia
authors.initials: S
authors.lastname: Barluenga
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Winfried
authors.initials: W
authors.lastname: Römer
authors.forename: Nicolas
authors.initials: N
authors.lastname: Winssinger
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D005697:Galactosides / Q000737:chemistry*; D054884:Host-Pathogen Interactions; D008024:Ligands; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D018829:Adhesins, Bacterial; D005697:Galactosides; C102929:LecA protein, bacteria; D008024:Ligands
keywords: LecA; P. aeruginosa; bacterial invasion; glycan array; lectins