The peptide antibiotic clavanin A interacts strongly and specifically with lipid bilayers.

In this study the interaction of the antimicrobial peptide clavanin A with phosphatidylcholine bilayers is investigated by DSC, NMR, and AFM techniques. It is shown that the peptide interacts strongly and specifically with the lipids, resulting in increased order-disorder phase transition temperatures, phase separation, altered acyl chain and headgroup packing, and a drastically changed surface morphology of the bilayer. These results are interpreted in terms of clavanin-specific interactions with lipids and are discussed in the light of the different mechanisms by which clavanin A can destroy the barrier function of biological membranes.

The role of the abundant phenylalanines in the mode of action of the antimicrobial peptide clavanin.

Clavanin A is a special antimicrobial peptide that acts at the level of the membrane via a pH-dependent mechanism. At neutral pH, clavanin disrupts biological and model membranes in a nonspecific manner, causing efflux of large molecules. At mildly acidic conditions, however, the peptide efficiently kills bacteria by permeabilizing their membrane most likely by interacting with proteins involved in proton translocation [Biochemistry 41 (2002) 7529].

Clavanin permeabilizes target membranes via two distinctly different pH-dependent mechanisms.

The pH dependence of the antimicrobial and membrane activity of clavanin A, a peptide antibiotic that is rich in histidines and glycines, was analyzed in growth and membrane leakage experiments. Clavanin A more effectively inhibited the growth of the test organism Lactobacillus sake when the pH of the medium was lowered. Whereas the wild-type peptide efficiently released fluorophores from unilamellar vesicles at neutral pH according to a nonspecific permeabilization mechanism, it did not permeabilize model bilayers at low pH.