Mode of action of lipid II-targeting lantibiotics

The antimicrobial action of bacteriocins from Gram-positive bacteria is based on interaction with the cytoplasmic membrane of sensitive bacteria. Models based on studies with artificial membrane systems propose that nisin forms wedge-like poration complexes in the membrane by electrostatic interaction between the positively charged C terminus of the peptide and anionic membrane phospholipids. Nisin can also permeabilise membranes via a targeted mechanism by using lipid 11, 1:he bactoprenol-bound precursor of the bacterial cell wall, as a docking molecule. Another consequence of binding with lipid 11 is the inhibition of peptidoglycan biosynthesis. Mersacidine and actagardine also form a complex with lipid 11, but binding only blocks the incorporation of lipid 11 into peptidoglycan, resulting in slow cell lysis rather than pore formation. Both peptides share a conserved sequence motif with plantaricin C and pediocin PD-1, which is most probably involved in the binding of these bacteriocins to lipid 11. Although pediocin PD-1 and plantaricin C may inhibit peptidoglycan biosynthesis, pore formation is rather due to electrostatic interaction between the positively charged unbridged N-terminus and anionic phospholipids in the cytoplasmic membrane of sensitive cells. In the light of increased antibiotic resistance, this review focuses on the mode of action of lantibiotics that involve lipid 11, possible candidates for the development of new-generation novel antibiotic drugs. (c) 2005 Elsevier B.V All rights reserved.