Different modes of antibiotic action of homodimeric and monomeric bactenecin, a cathelicidin-derived antibacterial peptide.
The bactenecin is an antibacterial peptide with an intramolecular disulfide bond. We recently found that homodimeric bactenecin exhibits more potent antibacterial activity than the monomeric form and retains its activity at physiological conditions. Here we assess the difference in the modes of antibiotic action of homodimeric and monomeric bactenecins. Both monomeric and dimeric bactenecins almost completely killed both Staphylococcus aureus and E. coli within 10-30 min at concentrations of 8-16 muM. However, exposure to liposomes elicited an increase in the fluorescence quantum yield from a tryptophan-containing monomeric analog, while the homodimeric analog showed a significant reduction in fluorescence intensity. Moreover, unlike the monomer, the homodimer displayed apparent membrane-lytic activity enabling release of various sized dyes from liposomes, and rapidly and fully depolarized the S. aureus membrane. Together, our results suggest that homodimeric bactenecin forms pores in the bacterial membrane, while monomeric one penetrates through the membrane to target intracellular molecules/organelles. [BMB reports 2009; 42(9): 586-592].
Department of Life Science, Research Center for Bio-imaging, Gwangju Institute of Science and Technology, Gwangju, Korea.
Ju Yeon
JY
Lee
Sung-Tae
ST
Yang
Hyo Jeong
HJ
Kim
Seung Kyu
SK
Lee
Hyun Ho
HH
Jung
Song Yub
SY
Shin
Jae Il
JI
Kim
D020106:Acrylamide / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D019281:Dimerization; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D005453:Fluorescence; D007700:Kinetics; D008051:Lipid Bilayers; D008081:Liposomes; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D014364:Tryptophan / Q000737:chemistry
D000890:Anti-Infective Agents; D008051:Lipid Bilayers; D008081:Liposomes; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C056454:bactenecin; D020106:Acrylamide; D012965:Sodium Chloride; D014364:Tryptophan