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 μg/ml, 1/4×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 μg/ml to <0.005 μg/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.
