High affinity surface binding of a strongly dimerizing vancomycin-group antibiotic to a model of resistant bacteria

The factors that give rise to binding enhancements when a strongly dimerizi ng vancomycin-group antibiotic (chloroeremomycin) binds to a model cell sur face of vancomycin-resistant enterococci (VRE) have been semiquantitated. T he model cell surface is comprised of vesicles to which have been anchored cell wall precursor analogues of vancomycin-resistant bacteria (which termi nate in -D-lactate) via a hydrophobic docosanoyl (C-22) chain. Using H-1 an d F-19 NMR spectroscopy, a large binding enhancement at the model cell surf ace (compared to the binding of an analogous ligand in free solution) has b een observed. This enhancement can be partitioned into two distinct factors : a simple concentrating factor arising from an-increase in local concentra tion of ligand when it is located at the vesicle surface and a factor arisi ng from the cooperative interaction of species mutually bound to the membra ne surface. The overall enhancement to binding at a surface compared to bin ding in free solution was found to be a factor of 10(2)-10(3). In contrast, no significant surface binding enhancement was observed for the weakly dim erizing antibiotic vancomycin.