Mode of action of the staphylococcinlike peptide Pep 5: voltage-dependent depolarization of bacterial and artificial membranes.
The cationic staphylococcinlike peptide Pep 5 is shown to depolarize bacterial and planar lipid membranes in a voltage-dependent manner. An artificial valinomycin-induced potassium diffusion potential across the cytoplasmic membrane of Staphylococcus cohnii 22 was sufficient to promote Pep 5 action. Thus, evidence is provided that a membrane potential of sufficient magnitude is the only prerequisite for Pep 5 activity. The voltage dependence was elucidated by macroscopic conductance measurements with black lipid membranes. A threshold potential of about -90 to -100 mV, which was deduced from experiments with bacterial cells, could be confirmed. Single pores were resolved which often occur as short-lived bursts and fluctuate among different conductance levels. Pore diameters were calculated ranging from 0.1 to 1 nm. Succinylation of the lysine residues of Pep 5 resulted in prolonged pore lifetimes and maintenance of distinct conductance levels. However, the succinylated peptide required a higher threshold potential, approximately -150 mV, than the native peptide, which is probably the reason for the reduced activity of the modified peptide against intact gram-positive bacteria.
Kordel
M
M
Institut für Medizinische Mikrobiologie und Immunologie, Universität Bonn, Bonn-Venusberg, Federal Republic of Germany.
Benz
R
R
Sahl
H G
HG
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001430:Bacteriocins / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D004553:Electric Conductivity; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000187:drug effects; D013210:Staphylococcus / Q000187:drug effects* / Q000378:metabolism; D013212:Staphylococcus epidermidis / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D008051:Lipid Bilayers; C017724:staphylococcin