In vitro synergistic potentials of novel antibacterial combination therapies against Salmonella Typhimurium, Escherichia coli and Staphylococcus aureus
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, Escherichia coli and Staphylococcus aureus were determined. Based on the FIC indexes 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 the Rattus norvegicus (IEC-6) cell line 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 (32–1024), (128–1024) and (512–≥2048) μg/mL, respectively. The FIC indexes of the combined antibacterials against these strains were 0.281–1.016. The ultrastructural morphology and time-kill assays 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 50% inhibitory concentrations (IC50) of GA and hamamelitannin in IEC-6 cells were 564.55 μM and 988.54 μM, respectively. Conclusions: The phenolic compounds increase the efficacy of existing antibiotics might be by disrupting virulence factors. We can conclude that these antibacterial combinations are safe and can be potential medications to treat S. Typhimurium, E. coli and S. aureus infections in animals and humans. 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.