In vitro synergistic potentials of novel antibacterial combination therapies against Salmonella Typhimurium and Escherichia coli
Abstract Background: Bacteria have remarkable abilities to acquire resistance against antibiotics by several mechanisms. New strategies are needed to block the development of resistance and to prolong the life of traditional antibiotics. This study aimed to increase the efficacy of existing antibiotics by combining them with the opportunistic phenolic compound gallic acid (GA) and its derivatives. Fractional inhibitory concentration (FIC) indexes of phenolic compound-antibiotic combinations against Salmonella enterica serovar Typhimurium ( S. Typhimurium) and Escherichia coli ( E. coli ) were determined. Based on the FIC index values and clinical importance, 3 combinations were selected to evaluate their effects on the virulence factors of these bacteria. The in vitro cytotoxicity of GA and hamamelitannin in human (Hep G2) and Rattus norvegicus (IEC-6) cell lines were evaluated. Results: Phenolic compounds demonstrated considerable antibacterial effects as the minimum inhibitory concentrations (MICs) of epigallocatechin, GA and hamamelitannin found against different strains were (512–1024), (256–1024) and (512–2048) μg/mL, respectively. The FIC indexes of the combined antibacterials against these strains were 0.281–1.016. The time-kill assays and ultrastructural morphology showed that the GA-ceftiofur combination, and hamamelitannin-erythromycin and GA-ampicillin combinations more efficiently inhibited the growth of S. Typhimurium and E. coli , respectively, compared to the individual antibiotics. Biofilm viability and the swimming and swarming motilities of S. Typhimurium in the presence of GA-ceftiofur and E. coli in the presence of the hamamelitannin-erythromycin and GA-ampicillin combinations were more competently inhibited than individual antimicrobials. The inhibitory concentrations 50% (IC 50 ) of GA and hamamelitannin in Hep G2 cells were 1427.34 μM and 2024.97 μM, and in IEC-6 cells were 564.55 μM and 988.54 μM, respectively. Conclusions: We can conclude that these antibacterial combinations can be potential medications to treat S. Typhimurium and E. coli infections. Further study to confirm this effect in in vivo system and to determine the precise mechanism of action should be undertaken to establish these combinations as medications.