(p)ppGpp Controls Bacterial Persistence by Stochastic Induction of Toxin-Antitoxin Activity (Retracted article. See vol. 172, pg. 1135, 2018)
(p)ppGpp Controls Bacterial Persistence by Stochastic Induction of Toxin-Antitoxin Activity (Retracted article. See vol. 172, pg. 1135, 2018)
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DOI：
10.1016/j.cell.2013.07.048
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发表时间：
2013-08-29
期刊：
影响因子：
64.5
通讯作者：
Gerdes, Kenn
中科院分区：
文献类型：
--
作者：
Maisonneuve, Etienne;Castro-Camargo, Manuela;Gerdes, Kenn
持久性是指对抗生素敏感的细菌等基因群体产生的罕见细胞瞬间变得耐多药的现象。在野生型细菌中，是否在一个罕见的细胞亚群中缓慢生长是持久性表型的基础尚未得到检验。在这里，我们展示了一个呈指数增长的野生型大肠杆菌细胞群体产生了罕见的细胞，这些细胞随机地转变为缓慢生长的细胞，这种缓慢生长的细胞具有多药耐受性，并且它们能够复苏。持久性表型在层次上取决于信号核苷酸(p)ppGpp， Lon蛋白酶，无机多磷酸盐和毒素-抗毒素。我们发现(p)ppGpp水平在指数生长的细胞群体中随机变化，而在罕见的细胞中，高(p)ppGpp水平诱导缓慢的生长和持久性。(p)ppGpp通过依赖无机多磷酸盐和Lon蛋白酶的调控级联激活毒素-抗毒素位点，从而触发缓慢生长。
Persistence refers to the phenomenon in which isogenic populations of antibiotic-sensitive bacteria produce rare cells that transiently become multidrug tolerant. Whether slow growth in a rare subset of cells underlies the persistence phenotype has not be examined in wild-type bacteria. Here, we show that an exponentially growing population of wildtype Escherichia coli cells produces rare cells that stochastically switch into slow growth, that the slow-growing cells are multidrug tolerant, and that they are able to resuscitate. The persistence phenotype depends hierarchically on the signaling nucleotide (p)ppGpp, Lon protease, inorganic polyphosphate, and toxin-antitoxins. We show that the level of (p)ppGpp varies stochastically in a population of exponentially growing cells and that the high (p)ppGpp level in rare cells induces slow growth and persistence. (p)ppGpp triggers slow growth by activating toxin-antitoxin loci through a regulatory cascade depending on inorganic polyphosphate and Lon protease.