Verapamil increases the bacteriostatic and bactericidal effects of adriamycin on Escherichia coli

The purpose of this study was to evaluate the effect of verapamil on adriamycin-resistant and -sensitive Escherichia coli bacterial strains. Two E. coli strains: B-SR9 and K12-KL16 were incubated with adriamycin in various concentrations in the presence or absence of verapamil. Growth and killing rates were measured using optical densities and colonogenic assays. Transmembrane transport capacity was evaluated by measuring radioactively labelled leucine uptake and intracellular potassium concentrations. While adriamycin (ADR) showed both bacteriostatic and bactericidal effects upon the two bacterial strains, the K12 strain was significantly more resistant to the drug than its peer. Subtoxic concentrations of verapamil augmented these effects in both strains. Verapamil affected bacterial transmembrane transport activity and caused potassium leakage through the cell membrane. Simultaneous exposure to adriamycin and verapamil resulted in rapid, massive damage to membrane functions, indicating accelerated killing rate. The authors concluded that verapamil acts as a potentiator of adriamycin's cytotoxicity in E. coli bacteria in a manner similar to that in multidrug resistant mammalian tumour cells. This observation suggests that the mechanisms of resistance to the drug may be similar in both species.