A LecA Ligand Identified from a Galactoside‐Conjugate Array Inhibits Host Cell Invasion by Pseudomonas aeruginosa |
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| Authors: | Dr. Alexandre Novoa Dr. Thorsten Eierhoff Dr. Jérémie Topin Dr. Annabelle Varrot Dr. Sofia Barluenga Dr. Anne Imberty Prof. Winfried Römer Prof. Nicolas Winssinger |
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| Affiliation: | 1. Department of Organic Chemistry, University of Geneva (Switzerland);2. Institute of Biology II, Albert Ludwigs University Freiburg, Sch?nzlestrasse 1, 79104 Freiburg (Germany);3. BIOSS Centre for Biological Signalling Studies, Albert Ludwigs University Freiburg, Sch?nzlestrasse 18, 79104 Freiburg (Germany);4. CERMAV, Université Grenoble Alpes and CNRS, 38000 Grenoble (France) |
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| 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. |
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| Keywords: | bacterial invasion glycan array LecA lectins P. aeruginosa |
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