Understanding and Sensitizing Density-Dependent Persistence to Quinolone Antibiotics.
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Abstract | Physiologic and environmental factors can modulate antibiotic activity and thus pose a significant challenge to antibiotic treatment. The quinolone class of antibiotics, which targets bacterial topoisomerases, fails to kill bacteria that have grown to high density; however, the mechanistic basis for this persistence is unclear. Here, we show that exhaustion of the metabolic inputs that couple carbon catabolism to oxidative phosphorylation is a primary cause of growth phase-dependent persistence to quinolone antibiotics. Supplementation of stationary-phase cultures with glucose and a suitable terminal electron acceptor to stimulate respiratory metabolism is sufficient to sensitize cells to quinolone killing. Using this approach, we successfully sensitize high-density populations of Escherichia coli, Staphylococcus aureus, and Mycobacterium smegmatis to quinolone antibiotics. Our findings link growth-dependent quinolone persistence to discrete impairments in respiratory metabolism and identify a strategy to kill non-dividing bacteria. |
Year of Publication | 2017
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Journal | Mol Cell
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Volume | 68
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Issue | 6
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Pages | 1147-1154.e3
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Date Published | 2017 12 21
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ISSN | 1097-4164
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DOI | 10.1016/j.molcel.2017.11.012
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PubMed ID | 29225037
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