Phytochemicals increase the antibacterial activity of antibiotics by acting on a drug efflux pump.
Bottom Line: In silico screening was used to predict the bioactivity of plant compounds and to compare that with the known EPI, phe-arg-β-naphthylamide (PAβN).Subsequently, promising products have been tested for their ability to inhibit efflux.We demonstrated the feasibility of in silico screening to identify compounds that potentiate the action of antibiotics against drug-resistant strains and which might be potentially useful lead compounds for an EPI discovery program.
Affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, United Kingdom.Show MeSH
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Mentions: Ethidium, Hoechst 33342 and TMA-DPH all share the property that they are virtually nonfluorescent in aqueous solution while undergoing a large increase in fluorescent quantum yield when in a hydrophobic environment such as when in a lipid bilayer or intercalated into DNA. Hence, the passive permeation of these compounds into bacterial cells can be followed by the increase in their fluorescence. It is clear from Figure 1A–C that the fluorescence (and hence passive permeation) of all three fluorescent compounds are identical in E. coli cells which have been deenergized by the addition of the protonophore CCCP. Therefore, there is no intrinsic difference in permeability between the cells used in this study. However, when the cells are energized by the addition of glucose, there is a marked decrease in fluorescence between the wild type (resistant) and ΔAcrB cells (Fig. 1D–F). This decrease in fluorescence is representative of AcrB-mediated efflux of the fluorescent compounds. Combined, the results mean that any effects on the MICs for the test compounds observed would be due to the active AcrB-mediated efflux of the compounds and not due to intrinsic differences in the membrane permeability between the strains used in the study.
Affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, United Kingdom.