Metabolomic analysis of the mechanism of action of yerba mate extract on Salmonella Typhimurium

Background: Salmonella Typhimurium is a gram-negative enteropathogen that infects millions worldwide; the rapid emergence of antibiotic resistant strains has heightened the urgency of developing effective treatment for this pathogen. Previous studies have demonstrated that the aqueous extract of yerba mate (Ilex paraguariensis) provides effective therapy, in vitro, for the drug-resistant S. Typhimurium DT104. Unfortunately, while some of the chemical constituents that contribute to the extract’s antibacterial activity have been identified, the mechanism of action of the extract is still unknown and of crucial importance to its future potential in combating antibiotic resistant bacteria. Results: Yerba mate extract altered central carbon metabolism in S. Typhimurium, reduced catalase activity by means other than direct inhibition, and did not change membrane integrity (except at the initial 0 time point, where differences were not resolved) despite a significant increase in the production of a cell wall precursor. Additional significant differences were observed in the global metabolic regulators alpha-ketoglutarate and acetylphosphate, the energy-related molecule NAD+, and in an unexpected match to the antibacterial compound yohimbine. Conclusions: This work provides the first insight into the mechanism of action of yerba mate extract on S. Typhimurium by revealing a major impact on central carbon metabolism, catalase activity, and possible metabolic links to interference in energy production and membrane integrity. The putative identification of the antibacterial compound yohimbine and the many unidentified compounds provides additional avenues for future investigations of novel yerba mate compounds capable of traversing or binding to S. Typhimurium’s membrane.