Lactococcin G Is a Potassium Ion-Conducting, Two-Component Bacteriocin

Lactococcin G is a novel lactococcal bacteriocin whose activity depends on the complementary action of two peptides, termed α and β. Peptide synthesis of the α and β peptides yielded biologically active lactococcin G, which was used in mode-of-action studies on sensitive cells of Lactococcus lactis. Approximately equivalent amounts of both peptides were required for optimal bactericidal effect. No effect was observed with either the α or β peptide in the absence of the complementary peptide. The combination of α and β peptides (lactococcin G) dissipates the membrane potential (Δψ), and as a consequence cells release α-aminoisobutyrate, a non-metabolizable alanine analog that is accumulated through a proton motive-force dependent mechanism. In addition, the cellular ATP level is dramatically reduced, which results in a drastic decrease of the ATP-driven glutamate uptake. Lactococcin G does not form a proton-conducting pore, as it has no effect on the transmembrane pH gradient. Dissipation of the membrane potential by uncouplers causes a slow release of potassium (rubidium) ions. However, rapid release of potassium was observed in the presence of lactococcin G. These data suggest that the bactericidal effect of lactococcin G is due to the formation of potassium-selective channels by the α and β peptides in the target bacterial membrane.