The lantibiotic nisin, a special case or not?
Nisin is a 34-residue-long peptide belonging to the group A lantibiotics with antimicrobial activity against Gram-positive bacteria. The presence of dehydrated residues and lanthionine rings (thioether bonds) in nisin, imposing structural restrains on the peptide, make it an interesting case for studying the mode of action. In addition, the relatively high activity (nM range) of nisin against Gram-positive bacteria indicates that nisin may be a special case in the large family of pore-forming peptides antibiotics. In this review, we attempted to dissect the mode of action of nisin concentrating on studies that used model membranes or biological membranes. The picture that emerges suggests that in model membrane systems, composed of only phospholipids, nisin behaves similar to the antimicrobial peptide magainin, albeit with an activity that is much lower as compared to its activity towards biological membranes. This difference can be contributed to a missing factor which nisin needs for its high activity. Novel results have identified the factor as Lipid II, a precursor in the bacterial cell wall synthesis. The special high affinity interaction of nisin with Lipid II resulting in high activity and the active role of Lipid II in the pore-formation process make nisin a special case.
Breukink
E
E
Department of the Biochemistry of Membranes, Center for Biomembranes and Lipid Enzymology, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH, Utrecht, Netherlands.
de Kruijff
B
B
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D002473:Cell Wall / Q000737:chemistry; D006094:Gram-Positive Bacteria / Q000737:chemistry / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry; D008564:Membrane Potentials; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009561:Nisin / Q000737:chemistry* / Q000494:pharmacology; D010457:Peptidoglycan; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry; D011104:Polyisoprenyl Phosphate Oligosaccharides / Q000737:chemistry
D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D010457:Peptidoglycan; D010743:Phospholipids; D011104:Polyisoprenyl Phosphate Oligosaccharides; D009561:Nisin; C062770:undecaprenyl diphosphate-(N-acetylglucosaminyl)(1-4)-N-acetylmuramoyl pentapeptide