Bioenergetic stress potentiates antimicrobial resistance and persistence

Barry Li, Shivani Srivastava, Mustafa Shaikh, Gautam Mereddy, Madison R. Garcia, Eric N. Chiles, Avi Shah, Boatema Ofori-Anyinam, Ting-Yu Chu, Nicole J. Cheney, Douglas McCloskey, Xiaoyang Su and Jason H. Yang ()
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Barry Li: Rutgers New Jersey Medical School
Shivani Srivastava: Rutgers New Jersey Medical School
Mustafa Shaikh: Rutgers New Jersey Medical School
Gautam Mereddy: Rutgers New Jersey Medical School
Madison R. Garcia: Rutgers New Jersey Medical School
Eric N. Chiles: The State University of New Jersey
Avi Shah: Rutgers New Jersey Medical School
Boatema Ofori-Anyinam: Rutgers New Jersey Medical School
Ting-Yu Chu: Rutgers New Jersey Medical School
Nicole J. Cheney: Rutgers New Jersey Medical School
Douglas McCloskey: Technical University of Denmark
Xiaoyang Su: The State University of New Jersey
Jason H. Yang: Rutgers New Jersey Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract The bactericidal action of some antibiotics is associated with increased ATP consumption, cellular respiration, and reactive oxygen species (ROS) formation. Here, we investigate the effects of ‘bioenergetic stress’, induced by constitutive hydrolysis of ATP and NADH, on antibiotic efficacy in Escherichia coli. We show that bioenergetic stress potentiates the evolution of antibiotic resistance via enhanced ROS production, mutagenic break repair, and transcription-coupled repair. In addition, bioenergetic stress potentiates antibiotic persistence via the stringent response. We propose a model in which the balance between ATP consumption versus production regulates antibiotic resistance and persistence.

Date: 2025
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DOI: 10.1038/s41467-025-60302-6

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