title: Mechanism of action of dipropofol and synergistic action with other antibacterial agents in vitro.
abstract: The mode of action of dipropofol and its antibacterial activity in combination with other antibiotics against Gram-positive and -negative bacteria were investigated. Dipropofol showed a bactericidal effect against Staphylococcus aureus 209P, and inhibited the incorporations of 3H-glutamate and 3H-leucine into S. aureus 209P and Bacillus subtilis PCI219 cells. These results indicated that the mechanism of action of dipropofol was mediated by the inhibition of protein synthesis or amino acid incorporation. A synergistic effect was performed by checkerboard titration with Muller-Hinton agar plates containing dipropofol (0.39 microg/ml, 1/4 x MIC) and various concentrations of nine other antibiotics in vitro. The synergism against vancomycin resistant Enterococcus faecium was confirmed in the combination of dipropofol with rifampicin. The MIC of rifampicin was decreased from 0.39 microg/ml to <0.005 microg/ml by the addition of dipropofol. This combinational effect in reversing vancomycin resistance of enterococci highlights novel drug targets and has importance in the design of new therapeutic regimens against resistant pathogens.
authors.affiliation: Aomori University.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ogata
authors.forename: Takao
authors.initials: T
authors.lastname: Kunikane
authors.forename: Masako
authors.initials: M
authors.lastname: Seki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oka
authors.forename: Shiro
authors.initials: S
authors.lastname: Urano
authors.forename: Sachiko
authors.initials: S
authors.lastname: Seki
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Seki
authors.forename: Toyoshige
authors.initials: T
authors.lastname: Endo
mesh_terms: D000473:Alkanes / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D004357:Drug Synergism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010636:Phenols / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics; D020713:Vancomycin Resistance
chemical_list: D000473:Alkanes; D000596:Amino Acids; D000900:Anti-Bacterial Agents; D010636:Phenols; D011500:Protein Synthesis Inhibitors; C504748:dipropofol