Metabolomic analysis of the mechanism of action of yerba mate aqueous extract on Salmonella enterica serovar Typhimurium
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Salmonella enterica serovar Typhimurium is a Gram-negative enteropathogen that infects millions of people worldwide each year; the emergence of drug-resistant strains has heightened the need for novel treatments. Aqueous extracts of yerba mate (Ilex paraguariensis) effectively inhibit drug-resistant S. Typhimurium in vitro. Some chemical constituents that contribute to the extract’s antibacterial activity have been identified, but the mechanism of action of the extract is still unknown.
This study sought to gain insight into the antibacterial mechanism of yerba mate extract against S. Typhimurium.
Assays for catalase activity and membrane permeability were used to select time points for an LC-MS metabolomics analysis of S. Typhimurium intracellular components.
Yerba mate extract induced changes in central carbon metabolism in S. Typhimurium, reduced catalase activity by means other than direct inhibition, and did not change membrane integrity 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.
This work provides the first evaluation of the mechanism of action of yerba mate extract on S. Typhimurium, 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 yerba mate compounds capable of traversing or binding to S. Typhimurium’s membrane.
KeywordsYerba mate Antibacterial Natural product Salmonella enterica serovar Typhimurium Metabolomics
We are very grateful for the use of Dr. P. Michael Davidson’s BSL-2 laboratory, equipment, and storage space. We would also like to thank the Department of Food Science and Technology for the use of S. Typhimurium DT104 strain 2576, Dr. Hayriye Bozkurt for assistance with BSL-2 lab equipment, Dr. Arnold Saxton for statistics advice, and Dr. Shawn Campagna, Dr. Hector Castro Gonzalez, and Eric Tague for extracting and running samples for metabolomics. This research was supported by the Ivan Racheff Chair of Excellence endowment and the Graduate School of Genome Science and Technology.
CSR, SCL, KPB, and CNS conceived and designed the study; CSR conducted the experiments, CSR and SCL analyzed and interpreted the data; CSR, SCL, KPB, and CNS wrote and edited the manuscript. All authors read and approved the final manuscript.
Availability of supporting data
The data set supporting the results of this article is available in the MetaboLights repository, identifier MTBLS359; http://www.ebi.ac.uk/metabolights/MTBLS359.
Compliance with ethical standards
Conflict of interest
The authors (CSR, SCL, KPB, and CNS) declare that they have no competing interests.
Research involving human participants and/or animals
No human participants or animals were involved in this study.
No human participants were involved in this study.
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