4.7 Article

Metabolites in the TCA Cycle Promote Resistance to Chloramphenicol of Edwardsiella tarda

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 20, Issue 1, Pages 972-981

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.0c00725

Keywords

antibiotic resistance; Edwardsiella tarda; chloramphenicol; TCA cycle; redox

Funding

  1. Shandong Provincial Natural Science Foundation of China [ZR2019PC009]
  2. Key research project of Shandong province [2018GNC110034]
  3. Agricultural Seed Project of Shandong Province [2019LZGC013]
  4. Guangdong Provincial Natural Science Foundation of China [2019A1515012211]

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Metabolites in the TCA cycle increase the viability of bacteria against chloramphenicol, while NADPH promotes antibiotic resistance and oxidants restore the bactericidal ability. Additionally, the intracellular redox state determines the sensitivity to chloramphenicol, and the total antioxidative capacity is significantly reduced in antibiotic-resistant strains. These findings suggest that metabolite adjuvants should be cautiously applied, as they promote resistance to antibiotics.
Antibiotic-resistant bacteria are a serious threat to human and animal health. Metabolite-enabled eradication of drug-resistant pathogens is an attractive strategy, and metabolite adjuvants, such as fumarate, are used for restoring the bactericidal ability of antibiotics. However, we show that metabolites in the TCA cycle increase the viability of Edwardsiella tarda against chloramphenicol (CAP), based on the survival assay of differential metabolites identified by LC-MS/MS. Furthermore, NADPH promotes CAP resistance in the CAP-resistant strain, while oxidants restore the bactericidal ability. Finally, we show that the intracellular redox state determines the sensitivity to CAP, and the total antioxidative capacity is decreased significantly in the antibiotic-resistant strain. Considering that the metabolites promote CAP resistance, metabolite adjuvants should be applied very cautiously. Overall, our research expands on the knowledge that the redox state is related to the bactericidal ability of CAP.

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