Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria

Ashraf Zarkan, H-R Macklyne, Dimitri Chirgadze, Andrew Bond, AR Hesketh & H-J Hong
Vancomycin is known to bind to Zn(II) and can induce a zinc starvation response in bacteria. Here we identify a novel polymerization of vancomycin dimers by structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction. Bioassays indicate that this structure is associated with an increased antibiotic activity against bacterial strains possessing high level vancomycin resistance mediated by the reprogramming of peptidoglycan biosynthesis to use precursors terminating in D-Ala-D-Lac in place of D-Ala-D-Ala. Polymerization occurs via...
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