Resistance to antibiotics is increasing in some groups of clinically import
ant pathogens. For instance, high vancomycin resistance has emerged in ente
rococci. Promising alternative antibiotics are the peptide antibiotics, abu
ndant in host defense systems, which kill their targets by permeabilizing t
he plasma membrane, These peptides generally do not act via specific recept
ors and are active in the micromolar range. Here it is shown that vancomyci
n and the antibacterial peptide nisin Z use the same target: the membrane-a
nchored cell wall precursor Lipid II, Nisin combines high affinity for Lipi
d II with its pore-forming ability, thus causing the peptide to be highly a
ctive (in the nanomolar range).