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Published on: July 2, 2013
Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production
Mark P Brynildsen1, Jonathan A Winkler, Catherine S Spina
1Howard Hughes Medical Institute, Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Nature Biotechnology
|January 8, 2013
Summary
Targeting microbial reactive oxygen species (ROS) production can enhance antibiotic effectiveness against resistant infections. This study developed a systems-based method to boost ROS, increasing bacterial susceptibility to antibiotics and oxidants.
Area of Science:
- Microbiology
- Systems Biology
- Drug Discovery
Background:
- Antibiotic resistance is a growing global health crisis due to rising infections and a limited new drug pipeline.
- Antibiotics combat bacteria partly by inducing reactive oxygen species (ROS).
Purpose of the Study:
- To explore strategies for potentiating antibiotic activity by targeting microbial ROS production.
- To develop a predictive, systems-based method for enhancing bacterial ROS generation.
Main Methods:
- Utilized an ensemble approach of genome-scale metabolic models to predict ROS production in Escherichia coli.
- Systematically perturbed the metabolic network and analyzed flux distribution to identify targets for increased ROS.
- Experimentally validated in silico-predicted targets.
Main Results:
- Successfully demonstrated predictable enhancement of ROS production in E. coli.
- Validated targets increased bacterial susceptibility to both oxidants and existing antibiotics.
- Established a systems-based method to tune microbial ROS production.
Conclusions:
- Increasing microbial ROS production can enhance susceptibility to oxidants and antibiotics.
- This approach offers a novel strategy to combat antibiotic-resistant infections.
- Systems biology provides a powerful tool for optimizing antimicrobial therapies.
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