Recreating the specific colicin N–Ra-LPS interaction in a model bacterial outer membrane

The Gram negative bacterial outer membrane protects the bacterium from external toxins such as antibiotics. This is partially responsible for Gram negative bacteria becoming the greatest emerging source of antibiotic resistance. The outer membrane is itself the target of some antibacterial agents such as polymixins but even these are subject to resistance mechanisms. We recently discovered that another antibacterial protein, colicin N, binds to the outer membrane lipid in a novel way that centres on the core oligosaccharide rather than the anionic phosphate groups targeted by the polymyxin family. In a recent paper we showed the importance of electrostatics in this binding and revealed that specific binding needed faults in the outer membrane model which expose the binding site. In this project we hope to define how exposure of the sugars allows for specific membrane binding.