Details

Autor(en) / Beteiligte

• Peng, Bo
• Su, Yu-bin
• Li, Hui
• Han, Yi
• Guo, Chang
• Tian, Yao-mei
• Peng, Xuan-xian

Titel

Exogenous Alanine and/or Glucose plus Kanamycin Kills Antibiotic-Resistant Bacteria

Ist Teil von

• Cell metabolism, 2015-02, Vol.21 (2), p.249-262

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Glucose and alanine abundances are suppressed in kanamycin-resistant E. tarda•Alanine or glucose, via the TCA cycle, restores bacterial susceptibility to antibiotics•NADH and proton motive force increases, which stimulates uptake of antibiotic•A functional metabolomics-based strategy to kill bacteria is developed Peng et al. show that exogenous alanine and/or glucose restores susceptibility to antibiotics in antibiotic-resistant bacteria by increasing TCA flux, NADH production, and proton motive force to enhance kanamycin uptake, both in vitro and in a mouse model for urinary tract infection.