Understanding and Sensitizing Density-Dependent Persistence to Quinolone Antibiotics

• DOI: 10.1016/j.molcel.2017.11.012
• Publication Date: 2017-12-08T14:22:48Z
• Authors: Arnaud Gutierrez; Saloni Jain; Prerna Bhargava; Meagan Hamblin; Michael A. Lobritz; James J. Collins
• Keywords: Persistence (discontinuity); Quinolone

Physiologic and environmental factors can modulate antibiotic activity thus pose a significant challenge to treatment. The quinolone class of antibiotics, which targets bacterial topoisomerases, fails kill bacteria that have grown high density; however, the mechanistic basis for this persistence is unclear. Here, we show exhaustion metabolic inputs couple carbon catabolism oxidative phosphorylation primary cause growth phase-dependent antibiotics. Supplementation stationary-phase cultures with glucose suitable terminal electron acceptor stimulate respiratory metabolism sufficient sensitize cells killing. Using approach, successfully high-density populations Escherichia coli, Staphylococcus aureus, Mycobacterium smegmatis Our findings link growth-dependent discrete impairments in identify strategy non-dividing bacteria.