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ACS Chem Biol. 2018 Aug 17;13(8):2106-2113. doi: 10.1021/acschembio.8b00271. Epub 2018 Jul 2.

Solid State NMR Studies of Intact Lipopolysaccharide Endotoxin.

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Université Grenoble Alpes, CNRS, CEA, IBS , F-38000 Grenoble , France.
University of Naples Federico II , Department of Chemical Sciences , via cintia 4 , Napoli , Italy.
University of Milano , Department of Pharmacological and Biomolecular Sciences , Via Balzaretti 9 , Milano , Italy.


Lipopolysaccharides (LPS) are complex glycolipids forming the outside layer of Gram-negative bacteria. Their hydrophobic and heterogeneous nature greatly hampers their structural study in an environment similar to the bacterial surface. We have studied LPS purified from E. coli and pathogenic P. aeruginosa with long O-antigen polysaccharides assembled in solution as vesicles or elongated micelles. Solid-state NMR with magic-angle spinning permitted the identification of NMR signals arising from regions with different flexibilities in the LPS, from the lipid components to the O-antigen polysaccharides. Atomic scale data on the LPS enabled the study of the interaction of gentamicin antibiotic bound to P. aeruginosa LPS, for which we could confirm that a specific oligosaccharide is involved in the antibiotic binding. The possibility to study LPS alone and bound to a ligand when it is assembled in membrane-like structures opens great prospects for the investigation of proteins and antibiotics that specifically target such an important molecule at the surface of Gram-negative bacteria.

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