Source: School of Life Sciences
Written by: School of Life Sciences
Edited by: Wang Dongmei

Very recently, a research paper titled “Exogenous Alanine and/or Glucose plus Kanamycin Kills Antibiotic-Resistant Bacteria” has been published in Cell Metabolism (2015,3;21(2):249-261) by Professor Xuan-xian Peng’s group, School of Life Sciences, Sun Yat-sen University, China. This paper proposes a new idea based on antibiotic-resistant metabolic status and develops a new approach using the existing antibiotics to control multidrug-resistant bacteria.

At present, the control of multidrug-resistant bacteria mainly depends upon the development of new antibiotics. However, the development becomes more and more difficult as the duration is time-consuming, and the use of new antibiotics easily leads to the new resistance, even selecting antibiotic-resistant superbugs. Therefore, how to control multidrug-resistant bacteria becomes a very concerned research area in the world.

The study reveals varied metabolomes between antibiotic-resistant and antibiotic-susceptible Edwardsiella tarda and identifies greatly depressed abundance of alanine and glucose in the antibiotic-resistant bacteria. Further results show that 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.

A comment was made by Professor James J. Collins in Harvard University in the same journal (Cell Metabolism, 2015,3;21(2):154-155). He said: "Investigating the relationships between bacterial metabolism and antibiotic sensitivity can help to uncover novel strategies for treating infections. The report by Peng et al. highlights the significance of the metabolic environment in antibiotic resistance and treatment strategies (Peng et al., 2015). It will be important to build upon this work and examine how the metabolic state varies with different resistance mechanisms and across different environmental conditions. Further studies may allow us to develop generalized metabolic therapeutics as co-treatments for already-prescribed antibiotics, thereby expanding a rapidly shrinking arsenal of effective therapies against resistant and persistent infections."