The ways peptide antibiotics can kill bacteria by interacting with specific lipids
Abstract number: C4-001
Kruijff B.
In this lecture the mode of membrane action of lantibiotics will be described. Lantibiotics are polypeptides that kill bacteria. They contain special ring structures that are closed by lanthionine residues. One well-studied lantibiotic is nisin that kills bacteria by targeted pore formation using Lipid II as receptor [1]. Lipid II consists of a bactoprenol chain that is linked via a pyrophosphate to a disaccharide containing a pentapeptide. The latter moiety is the building block for the peptidoglycan synthesis. The N-terminal part of nisin docks on the pyrophosphate unit of Lipid II [2] after which nisin becomes inserted into the membrane and assembles together with Lipid II in a transmembrane pore complex consisting of 8 nisin and 4 Lipid II molecules. Surprisingly, nisin variants and related lantibiotics that effectively kill bacteria and specifically dock on Lipid II do not form pores in the membrane and thus must use another mechanism to kill bacteria. We discovered by fluorescence microscopy that they remove Lipid II in the bacterial membranes from its functional location (septum, spiral zones) to other places in the membrane thereby inhibiting cell growth and division. These studies reveal that the lantibiotics are promising candidates for the development of new antibiotics that are highly needed with the alarming rise of drug resistant bacteria.
References
1. Breukink et al. Science 1999; 286: 2361–2364.
2. Hsu et al. Nat Struct Mol Biol 2004; 11: 963–967.
| Subject: |
C4–Lipid-protein Interactions in Membrane |
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