Metabolomics of
| Autor: | Sandra M, Carvalho, Joana, Marques, Carlos C, Romão, Lígia M, Saraiva |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Aconitate Hydratase
Carbon Monoxide Magnetic Resonance Spectroscopy Nitrogen Citric Acid Cycle Glutamate Synthase Glutamic Acid Gene Expression Regulation Bacterial Anti-Bacterial Agents Fumarate Hydratase Fumarates Escherichia coli Organometallic Compounds Ketoglutaric Acids Metabolomics Glycolysis Oxidation-Reduction Mechanisms of Action: Physiological Effects |
| Zdroj: | Antimicrobial agents and chemotherapy. 63(10) |
| ISSN: | 1098-6596 |
| Popis: | In the last decade, carbon monoxide-releasing molecules (CORMs) have been shown to act against several pathogens and to be promising antimicrobials. However, the understanding of the mode of action and reactivity of these compounds on bacterial cells is still deficient. In this work, we used a metabolomics approach to probe the toxicity of the ruthenium(II) complex Ru(CO)(3)Cl(glycinate) (CORM-3) on Escherichia coli. By resorting to (1)H nuclear magnetic resonance, mass spectrometry, and enzymatic activities, we show that CORM-3-treated E. coli accumulates larger amounts of glycolytic intermediates, independently of the oxygen growth conditions. The work provides several evidences that CORM-3 inhibits glutamate synthesis and the iron-sulfur enzymes of the tricarboxylic acid (TCA) cycle and that the glycolysis pathway is triggered in order to establish an energy and redox homeostasis balance. Accordingly, supplementation of the growth medium with fumarate, α-ketoglutarate, glutamate, and amino acids cancels the toxicity of CORM-3. Importantly, inhibition of the iron-sulfur enzymes glutamate synthase, aconitase, and fumarase is only observed for compounds that liberate carbon monoxide. Altogether, this work reveals that the antimicrobial action of CORM-3 results from intracellular glutamate deficiency and inhibition of nitrogen and TCA cycles. |
| Databáze: | OpenAIRE |
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