Antibacterial activity of honeys and potential synergism of honeys with antibiotics and alkaloid extract of Sophora alopecuroides plant against antibiotic-resistant Escherichia coli mutant

OBJECTIVE(S): The increase in multidrug-resistant Escherichia coli strains with an overactivated AcrAB-TolC efflux pump has reduced the effectiveness of synthetic antibiotics, such as ciprofloxacin. The activity of this efflux pump can be reduced by using natural products. This study aimed to use a combination of ciprofloxacin, honey, and alkaloid extract of Sophora alopecuroides against an E. coli mutant with an overactivated AcrAB-TolC pump. MATERIALS AND METHODS: First the physicochemical properties, total alkaloid content, antioxidant activity, and the minimum inhibitory concentration (MIC) of three local honey samples: Konar (lotus), Avishan (Thyme), and Gavan (Astragalus) were evaluated. Then, the MIC of different combinations of honey, ciprofloxacin, and plant alkaloid extract and expression of acrA and soxS genes were carried out using the agar dilution method and quantitative RT- PCR methods. RESULTS: The net absorbance, total alkaloid content, and DPPH radical scavenging activity of Konar honey were significantly higher than those of Avishan and Gavan honeys (P<0.05). However, the MIC of lotus honey was nearly similar to other honey types, and all honey (30% w/v)-ciprofloxacin combinations decreased the viability of mutant more than ciprofloxacin alone. A synergistic interaction (FICI =0.48) was observed in triplex complex of ciprofloxacin (10 µg/ml), honey (20% w/v), and plant extract (1 mg/ml). A significant decrease (P<0.05) in the expression level of genes was seen in the presence of the triplex complex. CONCLUSION: It is concluded that the interaction between honey and plant alkaloid extract enhanced the anti-pump activity and reduced the oxidative stress response of the E. coli mutant.