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Growth of Mycobacterium tuberculosis Biofilms
Published on: February 15, 2012
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.
Abstract:
Persisters, stochastic dormant variants of normal bacteria cell, represent a significant portion of the survivors upon exposure to antibiotics and other environmental stresses, which contributes substantially to high level antibiotics tolerance. Glutamine is a crucial component of the Mycobacteria nitrogen pool that is indispensable for survival upon stresses. To study whether a synergistic effect exists between glutamine and antibiotics against Mycobacterial persisters, the efficacy of rifampicin alone or together with exogenous glutamine upon Mycobacterium smegmatis mc2 155 persisters was monitored. The result showed that glutamine decreases M. smegmatis tolerance to rifampicin upon starvation. The reactive oxygen species level of the strains treated with rifampicin and glutamine increased. The synergism of glutamine and rifampicin to kill persisters might derive from altering the oxidative phosphorylation and TCA cycle, as both evidenced by both ATP level increase and transcriptome change. Glutamine might represent a synergistic agent of rifampicin to kill Mycobacteria persisters.
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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