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Sensitizing Escherichia coli for Erythromycin

Erythromycin belongs to the macrolide antibiotics and is mainly used for the treatment of infections caused by Gram-positive bacteria. It is an inhibitor of bacterial protein synthesis and has bacteriostatic effects. Escherichia coli is resistant against erythromycin, because the outer membrane and the efficient drug efflux pump protein system AcrAB – TolC prevent the accumulation of sufficiently high intracellular compound concentrations. Thus we established a phenotypic screen to identify sensitizers of E. coli for erythromycin. Active compounds showed a concentration-dependent activity and increased the activity of additional antibiotics besides erythromycin. Follow-up studies showed that active compounds reduced the activity of the efflux pumps, but also permeated the outer membrane. 

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