title: Fructose restores susceptibility of multidrug-resistant Edwardsiella tarda to kanamycin.
abstract: Edwardsiella tarda, the causative agent of Edwardsiellosis, imposes medical challenges in both the clinic and aquaculture. The emergence of multidrug resistant strains makes antibiotic treatment impractical. The identification of molecules that facilitate or promote antibiotic efficacy is in high demand. In the present study, we aimed to identify small molecules whose abundance is correlated with kanamycin resistance in E. tarda by gas chromatography-mass spectrometry. We found that the abundance of fructose was greatly suppressed in kanamycin-resistant strains. The incubation of kanamycin-resistant bacteria with exogenous fructose sensitized the bacteria to kanamycin. Moreover, the fructose also functioned in bacteria persisters and biofilm. The synergistic effects of fructose and kanamycin were validated in a mouse model. Furthermore, the mechanism relies on fructose in activating TCA cycle to produce NADH, which generates proton motive force to increase the uptake of the antibiotics. Therefore, we present a novel approach in fighting against multidrug resistant bacteria through exploration of antibiotic-suppressed molecules.
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: Bo
authors: B
authors: Peng
authors: Yi
authors: Y
authors: Han
authors: Hui
authors: H
authors: Li
authors: Xuan-xian
authors: XX
authors: Peng
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D020609:Edwardsiella tarda / Q000187:drug effects*; D005632:Fructose / Q000494:pharmacology*; D007612:Kanamycin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D005632:Fructose; D007612:Kanamycin
keywords: E. tarda; TCA cycle; fructose; kanamycin; multidrug resistance