Theoretical and Experimental Insights into Lipopolysaccharides-Polymyxin B Interactions Using Genetically Modified Enterobacterial Strains

Abstract

The Gram-negative Outer Membrane Lipopolysaccharides (LPS) is the first molecular barrier of the antimicrobial peptide (AMP). Each LPS monomer is composed of a lipid-A and a polysaccharide chain of multiple modular-subunits with defined chemical structure and properties. There is great interest in understanding how AMP, like Polymyxin-B, associate and permeabilizate bacterial membranes; nevertheless, this process is poorly understood and further studies are needed. To understand the Polymyxin-B interaction with the LPS, we have combined molecular dynamics simulations of LPS containing-bilayers and in vivo and in vitro experimental assays using genetically modified Escherichia coli and Salmonella Typhimurium strains to display LPS of controlled chemotypes. The dynamical characterization of the Polymyxn-B interactions with LPS-subunits gives a new insight of their contribution to the outer membrane destabilization process, which is essential to develop new antibiotics strategies. Granted by FONDECYT N° 11130576.