Phenolic chalcones lead to ion leakage from Gram-positive bacteria prior to cell death

Abstract

Chalcones, valuable precursors for flavonoids, have important antibacterial and antifungal activities against bacteria, pathogens, harmful fungi and even antibiotic-resistant microorganisms that cause food spoilage and infectious diseases. It is widely known that chalcones target various vital metabolic pathways of the bacterial cells, but little is known about their action on the cell membrane integrity. In the present study, we studied the antibacterial activity of 12 different substituted chalcones in a comparative way and revealed that the phenolic chalcones are superior to other substituted derivatives against both Gram-negative and Gram-positive bacteria. We also demonstrate that the cell membrane is the first barrier that the chalcone molecules face for their action, and that phenolic chalcones increase ionic cell membrane permeability to a greater extent than the other substituted members. Especially, ion leakage can be detected at lower concentrations than the minimum inhibitory levels against Gram-positive bacteria. Phenolic chalcones are superior to other substituted derivatives in their antibacterial action and cause leakage of ions from Gram-positive bacteria even in concentrations lower than the inhibitory levels. Ion leakage from Gram-positive bacterial cytoplasm is prior to the membrane deformation and cell death. Thus, we propose that ion leakage contribute to the greater activity of phenolic chalcones in comparison to non-phenolic ones, on Gram-positive bacteria. Even though, disruption of metabolic pathways may be the principal mode of action of chalcones; in accord with our observations, we propose that the ion leakage precedes other inhibitory effects and contribute to the antibacterial action of phenolic chalcones.