title: Synergistic interaction of PMAP-36 and PRW4 with aminoglycoside antibiotics and their antibacterial mechanism.
abstract: The antimicrobial peptide PMAP-36 is a highly cationic and amphipathic α-helical peptide. PRW4 is a truncated analog that replaces paired lysine residues with tryptophan along the N-terminal and deletes the C-terminal hydrophobic tail of PMAP-36. Studies on the two peptides have already been performed. However, whether there is a synergistic effect with antibiotics has not been investigated, and the study of the antibacterial mechanism of the peptides is inadequate. In this study, antibiotic-peptide combinations were tested against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, and the confocal laser scanning microscopy (LSCM) and DNA gel retardation were measured. The results indicated synergy between the peptides and gentamicin when tested against E. coli [fractional lethal concentration (FLC) < 0.5]; partial synergy was observed between the peptides and gentamicin against S. aureus (0.5 < FLC < 1); and streptomycin showed no reaction with the peptides against E. coli and S. aureus (1 < FLC < 4). LSCM and DNA binding suggest that PMAP-36 was able to translocate across the bacterial membranes and interact with intracellular DNA, but PRW4 presented no DNA-binding ability. These results indicate that the combination of PMAP-36 and PRW4 with aminoglycosides may provide useful information for clinical application, and the antibacterial mechanism of peptides likely does not solely involve cytoplasmic-membrane permeabilization.
authors.affiliation: Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Zeyun
authors.initials: Z
authors.lastname: Wang
authors.forename: Licong
authors.initials: L
authors.lastname: Zhang
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Wei
authors.forename: Baoming
authors.initials: B
authors.lastname: Shi
authors.forename: Anshan
authors.initials: A
authors.lastname: Shan
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000378:metabolism; D004357:Drug Synergism; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli / Q000187:drug effects*; D018613:Microscopy, Confocal; D011485:Protein Binding; D011506:Proteins / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004269:DNA, Bacterial; C085474:PMAP-36; D011506:Proteins