Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic.
Resistance to antibiotics is increasing in some groups of clinically important pathogens. For instance, high vancomycin resistance has emerged in enterococci. Promising alternative antibiotics are the peptide antibiotics, abundant in host defense systems, which kill their targets by permeabilizing the plasma membrane. These peptides generally do not act via specific receptors and are active in the micromolar range. Here it is shown that vancomycin and the antibacterial peptide nisin Z use the same target: the membrane-anchored cell wall precursor Lipid II. Nisin combines high affinity for Lipid II with its pore-forming ability, thus causing the peptide to be highly active (in the nanomolar range).
Breukink
E
E
Center of Biomembranes and Lipid Enzymology, Department of Biochemistry of Membranes, Institute for Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.
Wiedemann
I
I
van Kraaij
C
C
Kuipers
O P
OP
Sahl
H G
HG
de Kruijff
B
B
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002473:Cell Wall / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008563:Membrane Lipids / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008837:Micrococcus / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D009561:Nisin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010457:Peptidoglycan; D011104:Polyisoprenyl Phosphate Oligosaccharides / Q000378:metabolism*; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D008563:Membrane Lipids; D010455:Peptides; D010457:Peptidoglycan; D011104:Polyisoprenyl Phosphate Oligosaccharides; D009561:Nisin; C062770:undecaprenyl diphosphate-(N-acetylglucosaminyl)(1-4)-N-acetylmuramoyl pentapeptide; D014640:Vancomycin; C071364:nisin Z