An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II.
Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II-targeted lantibiotics are too short to be able to span the lipid bilayer and cannot form pores, but somehow they maintain their antibacterial efficacy. We describe an alternative mechanism by which members of the lantibiotic family kill Gram-positive bacteria by removing lipid II from the cell division site (or septum) and thus block cell wall synthesis.
Hasper
Hester E
HE
Department of Biochemistry of Membranes, Bijvoet Center for Biomolecular Research, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH, Utrecht, Netherlands.
Kramer
Naomi E
NE
Smith
James L
JL
Hillman
J D
JD
Zachariah
Cherian
C
Kuipers
Oscar P
OP
de Kruijff
Ben
B
Breukink
Eefjan
E
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001407:Bacillus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D001410:Bacillus megaterium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001412:Bacillus subtilis / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001430:Bacteriocins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002473:Cell Wall / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D008567:Membranes, Artificial; D009561:Nisin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010457:Peptidoglycan / Q000096:biosynthesis; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D014640:Vancomycin / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010455:Peptides; D010457:Peptidoglycan; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; C112560:mutacin 1140; D009561:Nisin; D014640:Vancomycin; C102526:nisin A