The Synergistic Effect of Exogenous Glutamine and Rifampicin Against Mycobacterium Persisters

Xue Huang1, Xiangke Duan1, Jiang Li1

  • 1Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Chongqing, China.

Insights

Glutamine reduces Mycobacterium smegmatis tolerance to rifampicin, enhancing antibiotic efficacy against persisters. This suggests glutamine may act synergistically with rifampicin to eliminate persister cells.

Area of Science:

  • Microbiology
  • Bacteriology
  • Drug Discovery

Background:

  • Bacterial persisters are dormant cells contributing to antibiotic tolerance.
  • Glutamine is essential for Mycobacterium survival under stress.
  • Understanding persister cell survival mechanisms is crucial for effective antibiotic treatment.

Purpose of the Study:

  • To investigate the synergistic effect of glutamine and rifampicin on Mycobacterium smegmatis persisters.
  • To determine if glutamine influences antibiotic tolerance in persister cells.

Main Methods:

  • Monitoring the efficacy of rifampicin alone and with exogenous glutamine against M. smegmatis persisters.
  • Measuring reactive oxygen species (ROS) levels.
  • Assessing ATP levels and transcriptome changes.

Main Results:

  • Glutamine decreased M. smegmatis persister tolerance to rifampicin during starvation.
  • Combined treatment with rifampicin and glutamine increased ROS levels.
  • ATP levels and transcriptome alterations indicated changes in oxidative phosphorylation and the TCA cycle.

Conclusions:

  • Glutamine exhibits a synergistic effect with rifampicin in killing Mycobacterium persisters.
  • This synergism may involve the modulation of cellular energy metabolism and oxidative stress pathways.
  • Glutamine shows potential as an adjunct therapy to enhance rifampicin's efficacy against mycobacterial persisters.

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