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; Jason H. Yang

doi:10.1038/s41467-025-60302-6

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, Jason H. Yang

Robert Wood Johnson Medical School (RWJMS), Medicine, Division of Endocrinology

Rutgers, The State University

Research output: Contribution to journal › Article › peer-review

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.

Original language	American English
Article number	5111
Journal	Nature communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-60302-6
State	Published - Dec 2025

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-025-60302-6

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title = "Bioenergetic stress potentiates antimicrobial resistance and persistence",

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 {\textquoteleft}bioenergetic stress{\textquoteright}, 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.",

author = "Barry Li and Shivani Srivastava and Mustafa Shaikh and Gautam Mereddy and Garcia, \{Madison R.\} and Chiles, \{Eric N.\} and Avi Shah and Boatema Ofori-Anyinam and Chu, \{Ting Yu\} and Cheney, \{Nicole J.\} and Douglas McCloskey and Xiaoyang Su and Yang, \{Jason H.\}",

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doi = "10.1038/s41467-025-60302-6",

language = "American English",

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T1 - Bioenergetic stress potentiates antimicrobial resistance and persistence

AU - Li, Barry

AU - Srivastava, Shivani

AU - Shaikh, Mustafa

AU - Mereddy, Gautam

AU - Garcia, Madison R.

AU - Chiles, Eric N.

AU - Shah, Avi

AU - Ofori-Anyinam, Boatema

AU - Chu, Ting Yu

AU - Cheney, Nicole J.

AU - McCloskey, Douglas

AU - Su, Xiaoyang

AU - Yang, Jason H.

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

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Bioenergetic stress potentiates antimicrobial resistance and persistence

Abstract

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