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Bacterial persisters are a stochastically formed subpopulation of low-energy cells

作者:Sylvie Manuse, Yue Shan, Silvia J. Cañas-Duarte, Somenath Bakshi, Wei-Sheng W. Sun, Hirotada Mori, Johan Paulsson, Kim Lewis · 发表于:PLoS Biology · 年份:2021 · DOI:10.1371/journal.pbio.3001194 · 被引用次数:176 · 研究领域:Bacterial Genetics and Biotechnology、Bacterial biofilms and quorum sensing、Protein Structure and Dynamics

Persisters represent a small subpopulation of non- or slow-growing bacterial cells that are tolerant to killing by antibiotics. Despite their prominent role in the recalcitrance of chronic infections to antibiotic therapy, the mechanism of their formation has remained elusive. We show that sorted cells of Escherichia coli with low levels of energy-generating enzymes are better able to survive antibiotic killing. Using microfluidics time-lapse microscopy and a fluorescent reporter for in vivo ATP measurements, we find that a subpopulation of cells with a low level of ATP survives killing by ampicillin. We propose that these low ATP cells are formed stochastically as a result of fluctuations in the abundance of energy-generating components. These findings point to a general "low energy" mechanism of persister formation.