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Bioenergetic stress potentiates antimicrobial resistance and persistence

Author

Listed:
  • Barry Li

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Shivani Srivastava

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Mustafa Shaikh

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Gautam Mereddy

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Madison R. Garcia

    (Rutgers New Jersey Medical School
    The State University of New Jersey)

  • Eric N. Chiles

    (The State University of New Jersey)

  • Avi Shah

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Boatema Ofori-Anyinam

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Ting-Yu Chu

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Nicole J. Cheney

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

  • Douglas McCloskey

    (Technical University of Denmark
    BioMed X Institute)

  • Xiaoyang Su

    (The State University of New Jersey
    Rutgers Robert Wood Johnson Medical School)

  • Jason H. Yang

    (Rutgers New Jersey Medical School
    Rutgers New Jersey Medical School)

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.

Suggested Citation

  • 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 , 2025. "Bioenergetic stress potentiates antimicrobial resistance and persistence," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60302-6
    DOI: 10.1038/s41467-025-60302-6
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