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 ‘bioenergetic stress’, induced by constitutive hydrolysis of ATP and NADH, on antibiotic efficacy...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60302-6
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author 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
author_facet 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
author_sort Barry Li
collection DOAJ
description 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.
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issn 2041-1723
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publishDate 2025-06-01
publisher Nature Portfolio
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series Nature Communications
spelling doaj-art-53694ab169564ac4bbf2bbcb6a6aed3d2025-08-20T03:45:32ZengNature PortfolioNature Communications2041-17232025-06-0116111810.1038/s41467-025-60302-6Bioenergetic stress potentiates antimicrobial resistance and persistenceBarry Li0Shivani Srivastava1Mustafa Shaikh2Gautam Mereddy3Madison R. Garcia4Eric N. Chiles5Avi Shah6Boatema Ofori-Anyinam7Ting-Yu Chu8Nicole J. Cheney9Douglas McCloskey10Xiaoyang Su11Jason H. Yang12Center for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolCenter for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolCenter for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolCenter for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolCenter for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolRutgers Cancer Institute of New Jersey; Rutgers University, The State University of New JerseyCenter for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolCenter for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolCenter for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolCenter for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolNovo Nordisk Foundation Center for Biosustainability, Technical University of DenmarkRutgers Cancer Institute of New Jersey; Rutgers University, The State University of New JerseyCenter for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical SchoolAbstract 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.https://doi.org/10.1038/s41467-025-60302-6
spellingShingle 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
Bioenergetic stress potentiates antimicrobial resistance and persistence
Nature Communications
title Bioenergetic stress potentiates antimicrobial resistance and persistence
title_full Bioenergetic stress potentiates antimicrobial resistance and persistence
title_fullStr Bioenergetic stress potentiates antimicrobial resistance and persistence
title_full_unstemmed Bioenergetic stress potentiates antimicrobial resistance and persistence
title_short Bioenergetic stress potentiates antimicrobial resistance and persistence
title_sort bioenergetic stress potentiates antimicrobial resistance and persistence
url https://doi.org/10.1038/s41467-025-60302-6
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