High Affinity Surface Binding of a Strongly Dimerizing Vancomycin-Group Antibiotic to a Model of Resistant Bacteria

TLDR: The overall enhancement to binding at a surface compared to binding in free solution was found to be a factor of 10(2)-10(3).

Abstract: The factors that give rise to binding enhancements when a strongly dimerizing vancomycin-group antibiotic (chloroeremomycin) binds to a model cell surface of vancomycin-resistant enterococci (VRE) have been semiquantitated. The model cell surface is comprised of vesicles to which have been anchored cell wall precursor analogues of vancomycin-resistant bacteria (which terminate in -D-lactate) via a hydrophobic docosanoyl (C-22) chain. Using H-1 and F-19 NMR spectroscopy, a large binding enhancement at the model cell surface (compared to the binding of an analogous ligand in free solution) has been observed. This enhancement can be partitioned into two distinct factors: a simple concentrating factor arising from an-increase in local concentration of ligand when it is located at the vesicle surface and a factor arising from the cooperative interaction of species mutually bound to the membrane surface. The overall enhancement to binding at a surface compared to binding 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 dimerizing antibiotic vancomycin.