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.

Microbiology Spectrum
|October 26, 2023
PubMed
Abstract

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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