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Bioenergetic stress potentiates antimicrobial resistance and persistence
Barry Li1,2, Shivani Srivastava1,2, Mustafa Shaikh1,2
1Center for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ, USA.
Nature Communications
|June 9, 2025
Summary
Bioenergetic stress in E. coli enhances antibiotic resistance and persistence by increasing reactive oxygen species (ROS) and activating repair mechanisms. This study reveals how cellular energy balance impacts bacterial survival against antibiotics.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Antibiotic action can involve increased cellular energy demands, including ATP consumption, respiration, and reactive oxygen species (ROS) generation.
- Understanding factors influencing antibiotic resistance and persistence is crucial for combating bacterial infections.
Purpose of the Study:
- To investigate the impact of bioenergetic stress on antibiotic efficacy in Escherichia coli.
- To elucidate the mechanisms by which bioenergetic stress influences antibiotic resistance and persistence.
Main Methods:
- Induction of bioenergetic stress through constitutive hydrolysis of ATP and NADH in E. coli.
- Analysis of mechanisms including ROS production, mutagenic break repair, and transcription-coupled repair.
- Assessment of the stringent response in relation to antibiotic persistence.
Main Results:
- Bioenergetic stress potentiates the evolution of antibiotic resistance.
- Enhanced ROS production, mutagenic break repair, and transcription-coupled repair contribute to resistance under stress.
- Bioenergetic stress increases antibiotic persistence through activation of the stringent response.
Conclusions:
- Cellular bioenergetic status significantly modulates bacterial responses to antibiotics.
- A model is proposed where the ATP consumption/production balance regulates antibiotic resistance and persistence.
- Targeting cellular energy pathways could be a strategy to overcome antibiotic resistance.
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