Mode of action of an antibacterial peptide, KLKLLLLLKLK-NH2.

Previously, we reported that a synthetic undecapeptide, KLKLLLLLKLK-NH2, and its D-enantiomer have potent bactericidal activities against both Gram-positive and Gram-negative bacteria. Here we examined the mode of action of KLKLLLLLKLK-NH2 with special reference to its effect on bacterial membranes. We found that both the outer and inner membrane of Escherichia coli become permeable to low molecular mass substances when treated with this peptide. Under these conditions, the bacteria lost the ability to synthesize ATP and to transport proline, suggesting that their electrochemical membrane potential was disrupted. This peptide appears to form numerous channels in bacterial membranes that interfere with membrane functions, resulting in cell death.