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Published on: July 2, 2013
L-glutamine sensitizes Gram-positive-resistant bacteria to gentamicin killing
Lvyuan Fan1, Zhiyu Pan1, Yilin Zhong1
1Department of Cell Biology & Institute of Biomedicine National Engineering Research Center of Genetic Medicine, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology,Jinan University , Guangzhou, China.
Importance:
Methicillin-resistant Staphylococcus aureus (MRSA) infection severely threatens human health due to high morbidity and mortality; it is urgent to develop novel strategies to tackle this problem. Metabolites belong to antibiotic adjuvants which improve the effect of antibiotics. Despite reports of L-glutamine being applied in antibiotic adjuvant for Gram-negative bacteria, how L-glutamine affects antibiotics against Gram-positive-resistant bacteria is still unclear. In this study, L-glutamine increases the antibacterial effect of gentamicin on MRSA, and it links to membrane permeability and pH gradient (ΔpH), resulting in uptake of more gentamicin. Of great interest, reduced reactive oxygen species (ROS) by glutathione was found under L-glutamine treatment; USA300 becomes sensitive again to gentamicin. This study not only offers deep understanding on ΔpH and ROS on bacterial resistance but also provides potential treatment solutions for targeting MRSA infection.
Insights
L-glutamine enhances gentamicin
Area of Science:
- Microbiology and Infectious Diseases
- Drug Discovery and Development
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant global health threat due to its high morbidity and mortality.
- Antibiotic adjuvants, such as metabolites, can potentiate the efficacy of existing antibiotics.
- The role of L-glutamine as an antibiotic adjuvant against Gram-positive resistant bacteria remains largely unexplored.
Purpose of the Study:
- To investigate the effect of L-glutamine on the antibacterial activity of gentamicin against MRSA.
- To elucidate the mechanisms underlying L-glutamine's adjuvant effect, focusing on membrane permeability, pH gradient (ΔpH), and reactive oxygen species (ROS).
Main Methods:
- Assessing the synergistic antibacterial effect of L-glutamine and gentamicin on MRSA.
- Measuring changes in bacterial membrane permeability and ΔpH.
- Quantifying intracellular ROS levels under L-glutamine treatment.
Main Results:
- L-glutamine significantly enhanced the antibacterial efficacy of gentamicin against MRSA.
- This potentiation was associated with increased membrane permeability and disruption of the pH gradient (ΔpH), facilitating greater gentamicin uptake.
- L-glutamine treatment led to reduced reactive oxygen species (ROS) levels, restoring MRSA's sensitivity to gentamicin.
Conclusions:
- L-glutamine acts as an effective antibiotic adjuvant against MRSA by modulating membrane permeability, ΔpH, and ROS.
- Understanding the interplay between ΔpH and ROS in bacterial resistance offers new therapeutic avenues.
- This study provides a promising strategy for combating MRSA infections by combining gentamicin with L-glutamine.
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