2. Academic Validation
  3. Exogenous alanine and/or glucose plus kanamycin kills antibiotic-resistant bacteria

Exogenous alanine and/or glucose plus kanamycin kills antibiotic-resistant bacteria

  • Cell Metab. 2015 Feb 3;21(2):249-262. doi: 10.1016/j.cmet.2015.01.008.
Bo Peng 1,  Yu-Bin Su 2,  Hui Li 2,  Yi Han 2,  Chang Guo 2,  Yao-Mei Tian 2,  Xuan-Xian Peng 3
Affiliations

Affiliations

  • 1 Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, MOE Key Lab Aquat Food Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People's Republic of China; Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8197, USA.
  • 2 Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, MOE Key Lab Aquat Food Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
  • 3 Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, MOE Key Lab Aquat Food Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People's Republic of China. Electronic address: [email protected].
PMID: 25651179 DOI: 10.1016/j.cmet.2015.01.008
Abstract

Multidrug-resistant bacteria are an increasingly serious threat to human and animal health. However, novel drugs that can manage infections by multidrug-resistant bacteria have proved elusive. Here we show that glucose and alanine abundances are greatly suppressed in kanamycin-resistant Edwardsiella tarda by GC-MS-based metabolomics. Exogenous alanine or glucose restores susceptibility of multidrug-resistant E. tarda to killing by kanamycin, demonstrating an approach to killing multidrug-resistant bacteria. The mechanism underlying this approach is that exogenous glucose or alanine promotes the TCA cycle by substrate activation, which in turn increases production of NADH and proton motive force and stimulates uptake of Antibiotic. Similar results are obtained with Other Gram-negative bacteria (Vibrio parahaemolyticus, Klebsiella pneumoniae, Pseudomonas aeruginosa) and Gram-positive bacterium (Staphylococcus aureus), and the results are also reproduced in a mouse model for urinary tract Infection. This study establishes a functional metabolomics-based strategy to manage Infection by antibiotic-resistant bacteria.

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