期刊
JOURNAL OF PROTEOME RESEARCH
卷 14, 期 3, 页码 1612-1620出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr501285f
关键词
multidrug resistance; E. tarda; kanamycin; fructose; TCA cycle
资金
- National 12th Five-Year Technology Based Plan Topic [2012BAD17B02]
- Comra Fund Grant [D.Y.125-15-T-07]
- 973 Project [2012CB114406]
- National Nature Science Foundation of China [41276145, 31272702]
- Guangdong Provincial Science and Technology Projects [2012A031100004]
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.
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