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: The outer membrane permeabilizing effect of the natural products was assessed by examining the rate of hydrolysis of a chromogenic β-lactam, nitrocefin by intact cells of E. coli. Hydrolysis of nitrocefin by the β-lactamase releases a colored compound that can be measured at 490 nm. The rate of nitrocefin hydrolysis is limited by the rate of diffusion across the outer membrane, hence an increased rate of hydrolysis of nitrocefin would be indicative of outer membrane permeabilization (Lomovskaya et al. 2001). The effect of the natural products on the rate of nitrocefin hydrolysis was determined at concentrations, where they did not interfere with the A490 measurements. We observed no increase in the rate of nitrocefin hydrolysis in the presence of the natural products. We could therefore conclude that the synergism with known antibiotics observed was not due to secondary mechanisms such as membrane permeabilization (Fig. 4).
Affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, United Kingdom.