Indirect inhibitory activity of pyrogallol against the Tet(K) efflux pump by a membrane effect: In vitro and in silico approach

Abstract

Several pharmacological and biological activities of phenolic compounds have been reported in the literature. Some phenolic compounds have antibacterial properties, either alone or in combination with currently used antibiotics. With an increasing number of cases of bacterial infections caused by resistant bacteria, the search for more effective treatments has become critical. The goal of this study was to assess pyrogallol's ability to reverse bacterial resistance by inhibiting efflux pumps, as well as to validate its mechanism of interaction using computational dynamics. To determine the Minimum Inhibitory Concentration (MIC) of pyrogallol, broth microdilution tests were performed. The MIC reduction of tetracycline and ethidium bromide confirmed efflux pump inhibition. Pyrogallol showed direct activity against Staphylococcus aureus; however, the synergistic effect was observed only with the tested antibiotic, reducing its concentration from 128 μg/mL to 45.25 μg/mL, and this effect was not associated with efflux pump inhibition. According to molecular dynamics, this compound interacts with the surface of the bacterial membrane. However, more research is needed to identify potential mechanisms of interaction with existing antibiotics.