VanZ Reduces the Binding of Lipoglycopeptide Antibiotics to and Cells.

, a member of the glycopeptide resistance gene cluster, confers resistance to lipoglycopeptide antibiotics independent of cell wall precursor modification by the genes. Orthologs of are present in the genomes of many clinically relevant bacteria, including and ; however, genes are absent in . Here, we show that the expression of enterococcal paralogs in increases the minimal inhibitory concentrations of lipoglycopeptide antibiotics teicoplanin, dalbavancin, oritavancin and new teicoplanin pseudoaglycone derivatives. The reduction in the binding of fluorescently labeled teicoplanin to the cells suggests the mechanism of VanZ-mediated resistance. In addition, using a genomic gene knockout mutant of , we have shown that the ability of VanZ proteins to compromise the activity of lipoglycopeptide antibiotics by reducing their binding is a more general feature of VanZ-superfamily proteins.