title: Exogenous alanine and/or glucose plus kanamycin kills antibiotic-resistant bacteria.
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.
authors: 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.
authors: Bo
authors: B
authors: Peng
authors: 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.
authors: Yu-Bin
authors: YB
authors: Su
authors: 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.
authors: Hui
authors: H
authors: Li
authors: 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.
authors: Yi
authors: Y
authors: Han
authors: 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.
authors: Chang
authors: C
authors: Guo
authors: 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.
authors: Yao-Mei
authors: YM
authors: Tian
authors: 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: pxuanx@sysu.edu.cn.
authors: Xuan-Xian
authors: XX
authors: Peng
mesh_terms: D000409:Alanine / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007612:Kanamycin / Q000737:chemistry / Q000494:pharmacology*; D055432:Metabolomics; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D007612:Kanamycin; D005947:Glucose; D000409:Alanine