Bacterial persisters are a stochastically formed subpopulation of low-energy cells.
Bacterial persisters are a stochastically formed subpopulation of low-energy cells.
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DOI：
10.1371/journal.pbio.3001194
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发表时间：
2021-04
期刊：
影响因子：
9.8
通讯作者：
Lewis K
中科院分区：
文献类型：
--
作者：
Manuse S;Shan Y;Canas-Duarte SJ;Bakshi S;Sun WS;Mori H;Paulsson J;Lewis K
持久性代表了一小部分不生长或生长缓慢的细菌细胞，它们对抗生素的杀灭具有耐受性。尽管它们在慢性感染对抗生素治疗的抵抗中起着突出的作用，但它们的形成机制仍然难以捉摸。我们发现，具有低水平能量产生酶的大肠杆菌分选细胞能够更好地在抗生素杀死中存活。使用微流控延时显微镜和荧光报告体内ATP测量，我们发现，一个亚群的细胞与低水平的ATP生存杀死氨苄青霉素。我们认为，这些低ATP细胞是随机形成的，是产生能量的成分丰度波动的结果。这些发现指向一个一般的“低能量”持久性形成机制。Persisters代表了一小部分不生长或生长缓慢的细菌细胞，它们对抗生素的杀伤具有耐受性，但它们的形成机制仍然难以捉摸。本研究对E.大肠杆菌的研究表明，能量产生酶水平的随机异质性导致了一个对抗生素耐受的低ATP细胞亚群。
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. Persisters represent a small subpopulation of non- or slow-growing bacterial cells that are tolerant to killing by antibiotics, but the mechanism of their formation has remained elusive. This study of E. coli shows that stochastic heterogeneity in levels of energy-generating enzymes results in a subpopulation of cells with low ATP that are tolerant to antibiotics.
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