The outer membrane proteins OprG and OprH from Pseudomonas aeruginosa have been proposed to contribute to the unusual antibiotic resistance of these bacteria. In order to better understand their mechanism of antibiotic interaction, we have solved the structures of these two proteins by solution NMR spectroscopy. Both proteins form 8-stranded beta-barrels with flexible extracellular loops. Both NMR structures were obtained in DHPC micelles and supplemented with data obtained in lipid bicelles (DMPC:DMPS:DHPC:DHPS 27:9:3:1). The structures were improved by measuring paramagnetic relaxation enhancements. OprH was further shown biochemically and by NMR to interact strongly with lipopolysaccharide through several barrel and loop residues [Edrington JBC286:39211]. This interaction presumably strengthens the OM and reduces its permeability. By contrast OprG appears to form a classic channel for transport of hydrophobic compounds � perhaps including antibiotics � across the OM.

Insight into antibiotic resistance of Pseudomonas aeruginosa from the structures of the outer membrane proteins OprG and OprH

245th National Meeting (2013)

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