Antibacterial activity of high concentrations of carvedilol against Gram-positive and Gram-negative bacteria

Abstract

Many drugs used to treat non-infectious diseases have also shown excellent antibacterial activity or the ability to enhance the action of antibiotics. The aim of this study was to investigate the antibacterial activity of a popular β-blocker, carvedilol, and its mechanism of antibacterial action. The antibacterial activity of carvedilol was evaluated using the microdilution method and its influence on the viability of bacterial cells was investigated by the alamarBlue^® test. Changes in phospholipid and fatty acid composition were analysed using LC-MS/MS and GC-MS techniques. The permeability of bacterial cell membranes following exposure to carvedilol was studied using propidium iodide staining and confocal microscopy. The ability of the tested bacteria to degrade carvedilol was examined by LC-MS/MS. In this study, the antibacterial activity of carvedilol is described for the first time, with a decrease in the viability of all assayed bacteria observed following treatment with the β-blocker. Staphylococcus aureus and Staphylococcus epidermidis were found to be the most sensitive among the tested strains. Significant modifications to fatty acid composition were observed in S. aureus incubated with carvedilol. Moreover, the cell membrane permeability of bacteria incubated with carvedilol was higher for Gram-positive bacteria than for Gram-negative bacteria. Furthermore, Gram-negative Escherichia coli and Pseudomonas aeruginosa strains, which were highly resistant to carvedilol, exhibited an ability to eliminate carvedilol from the growth medium. In addition, three carvedilol metabolites were identified in E. coli and P. aeruginosa cultures. The antibacterial activity of carvedilol may suggest its potential usefulness in the synthesis of new antibacterial drugs.

Keywords: Antibacterial activity; Carvedilol; Drug inactivation; Mechanism of action; β-blocker.