Bioenergetic stress potentiates antimicrobial resistance and persistence

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Antimicrobial resistance (AMR) is a critical global health threat.
• Antibiotic treatment induces physiological stress in bacteria, including altered energy metabolism and reactive oxygen species (ROS) production.
• The direct impact of this
• Main_Methods: [
• Engineered a synthetic genetic system in *Escherichia coli* to constitutively hydrolyze ATP or NADH, simulating bioenergetic stress.
• Investigated the effects of induced bioenergetic stress on AMR evolution and antimicrobial persistence.
• Analyzed mechanisms including ROS production, mutagenic break repair, and transcription-coupled repair.

Purpose of the Study:

• To investigate the direct effects of bioenergetic stress on antibiotic efficacy.
• To understand how antibiotic-induced bioenergetic stress contributes to antimicrobial resistance and persistence.
• To elucidate the underlying molecular mechanisms linking bioenergetic stress to AMR.

Main Methods:

• Engineered a synthetic genetic system in *Escherichia coli* to constitutively hydrolyze ATP or NADH, simulating bioenergetic stress.
• Investigated the effects of induced bioenergetic stress on AMR evolution and antimicrobial persistence.
• Analyzed mechanisms including ROS production, mutagenic break repair, and transcription-coupled repair.

Main Results:

• Bioenergetic stress significantly potentiates AMR evolution.
• Mechanisms include enhanced ROS production, mutagenic break repair, and transcription-coupled repair.
• Bioenergetic stress also potentiates antimicrobial persistence through stringent response activation.

Conclusions:

• Antibiotic-induced bioenergetic stress is a key driver of both AMR evolution and persistence.
• This study proposes a unifying model for antibiotic-induced resistance and persistence.
• Findings have significant implications for strategies to combat AMR infections.