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18β-Glycyrrhetinic Acid Induces Metabolic Changes and Reduces Staphylococcus aureus Bacterial Cell-to-Cell Interactions

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Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT 59717, USA
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Department of Microbiology & Cell Biology, Montana State University, Bozeman, MT 59717, USA
*
Authors to whom correspondence should be addressed.
Current Affiliation: U.S. Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA.
Academic Editor: María Auxiliadora Dea-Ayuela
Antibiotics 2022, 11(6), 781; https://doi.org/10.3390/antibiotics11060781
Received: 18 May 2022 / Revised: 2 June 2022 / Accepted: 7 June 2022 / Published: 8 June 2022
The rise in bacterial resistance to common antibiotics has raised an increased need for alternative treatment strategies. The natural antibacterial product, 18β-glycyrrhetinic acid (GRA) has shown efficacy against community-associated methicillin-resistant Staphylococcus aureus (MRSA), although its interactions against planktonic and biofilm modes of growth remain poorly understood. This investigation utilized biochemical and metabolic approaches to further elucidate the effects of GRA on MRSA. Prolonged exposure of planktonic MRSA cell cultures to GRA resulted in increased production of staphyloxanthin, a pigment known to exhibit antioxidant and membrane-stabilizing functions. Then, 1D 1H NMR analyses of intracellular metabolite extracts from MRSA treated with GRA revealed significant changes in intracellular polar metabolite profiles, including increased levels of succinate and citrate, and significant reductions in several amino acids, including branch chain amino acids. These changes reflect the MRSA response to GRA exposure, including potentially altering its membrane composition, which consumes branched chain amino acids and leads to significant energy expenditure. Although GRA itself had no significant effect of biofilm viability, it seems to be an effective biofilm disruptor. This may be related to interference with cell–cell aggregation, as treatment of planktonic MRSA cultures with GRA leads to a significant reduction in micro-aggregation. The dispersive nature of GRA on MRSA biofilms may prove valuable for treatment of such infections and could be used to increase susceptibility to complementary antibiotic therapeutics. View Full-Text
Keywords: Staphylococcus aureus; antibacterials; antibiotics; resistance; staphyloxanthin; nuclear magnetic resonance; metabolomics; MRSA; planktonic cell cultures; biofilm infections Staphylococcus aureus; antibacterials; antibiotics; resistance; staphyloxanthin; nuclear magnetic resonance; metabolomics; MRSA; planktonic cell cultures; biofilm infections
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MDPI and ACS Style

Weaver, A.J., Jr.; Borgogna, T.R.; O’Shea-Stone, G.; Peters, T.R.; Copié, V.; Voyich, J.; Teintze, M. 18β-Glycyrrhetinic Acid Induces Metabolic Changes and Reduces Staphylococcus aureus Bacterial Cell-to-Cell Interactions. Antibiotics 2022, 11, 781. https://doi.org/10.3390/antibiotics11060781

AMA Style

Weaver AJ Jr., Borgogna TR, O’Shea-Stone G, Peters TR, Copié V, Voyich J, Teintze M. 18β-Glycyrrhetinic Acid Induces Metabolic Changes and Reduces Staphylococcus aureus Bacterial Cell-to-Cell Interactions. Antibiotics. 2022; 11(6):781. https://doi.org/10.3390/antibiotics11060781

Chicago/Turabian Style

Weaver, Alan J., Jr., Timothy R. Borgogna, Galen O’Shea-Stone, Tami R. Peters, Valérie Copié, Jovanka Voyich, and Martin Teintze. 2022. "18β-Glycyrrhetinic Acid Induces Metabolic Changes and Reduces Staphylococcus aureus Bacterial Cell-to-Cell Interactions" Antibiotics 11, no. 6: 781. https://doi.org/10.3390/antibiotics11060781

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