Synergistic effect of antimicrobial peptide arenicin-1 in combination with antibiotics against pathogenic bacteria.
Arenicin-1, a 21-mer antimicrobial peptide, has been known to exert broad bactericidal activity. In this study, the combination effect of arenicin-1 with conventional antibiotics was investigated and all combinations showed synergistic effects against bacterial strains (fractional inhibitory concentration index ≤ 0.75). In an assay using fluorescent dye 3'-(p-hydroxyphenyl) fluorescein (HPF) and hydroxyl radical scavenger thiourea, we demonstrated that combined treatments of arenicin-1 and antibiotics caused synergistic effects by producing hydroxyl radicals, particularly in bacterial strains treated with the peptide and ampicillin. The oxidative stress induced by arenicin-1 was stimulated by transient depletion of NADH. Flow cytometric analysis with propidium iodide (PI) indicated that MIC of arenicin-1 for combination continued to increase the permeability of the bacterial cytoplasmic membrane, enhancing the entry of erythromycin and chloramphenicol which act as protein synthesis inhibitors. Therefore, arenicin-1 synergizes with antibiotics by means of hydroxyl radical formation or membrane-active mechanisms. This combination therapy allows the use of lower concentrations of arenicin-1 and restores the effectiveness of antibiotics.
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-ku, Daegu 702-701, Republic of Korea.
Hyemin
H
Choi
Dong Gun
DG
Lee
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004357:Drug Synergism; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D015801:Helminth Proteins / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000032:analysis; D008826:Microbial Sensitivity Tests; D018384:Oxidative Stress
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D015801:Helminth Proteins; C496888:arenicin-1, Arenicola marina; D017665:Hydroxyl Radical