Li Barry, Srivastava Shivani, Shaikh Mustafa, Mereddy Gautam, Garcia Madison R, Chiles Eric N, Shah Avi, Ofori-Anyinam Boatema, Chu Ting-Yu, Cheney Nicole J, McCloskey Douglas, Su Xiaoyang, Yang Jason H
Center for Emerging and Re-emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ, USA.
Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, USA.
Nat Commun. 2025 Jun 9;16(1):5111. doi: 10.1038/s41467-025-60302-6.
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.
一些抗生素的杀菌作用与ATP消耗增加、细胞呼吸以及活性氧(ROS)生成有关。在此,我们研究了由ATP和NADH的组成性水解诱导的“生物能量应激”对大肠杆菌中抗生素功效的影响。我们发现,生物能量应激通过增强ROS产生、诱变断裂修复和转录偶联修复,增强了抗生素耐药性的演变。此外,生物能量应激通过严谨反应增强了抗生素耐受性。我们提出了一个模型,其中ATP消耗与产生之间的平衡调节抗生素耐药性和耐受性。