Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Richardson Road, Newcastle upon Tyne NE2 4AX, UK.
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Richardson Road, Newcastle upon Tyne NE2 4AX, UK.
Cell. 2013 Aug 29;154(5):1140-1150. doi: 10.1016/j.cell.2013.07.048.
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 wild-type 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.
持续性是指具有相同遗传背景的抗生素敏感菌产生短暂的多药耐药性的稀有细胞的现象。在野生型细菌中，尚未研究是否在细胞的稀有亚群中缓慢生长是持续性表型的基础。在这里，我们表明，野生型大肠杆菌细胞的指数增长群体产生了随机进入缓慢生长的稀有细胞，这些缓慢生长的细胞具有多药耐药性，并且能够复苏。持续性表型取决于信号核苷酸（p）ppGpp、Lon 蛋白酶、无机多磷酸盐和毒素-抗毒素的层次结构。我们表明，（p）ppGpp 在指数生长细胞的群体中随机变化，并且稀有细胞中的高（p）ppGpp 水平诱导缓慢生长和持续性。（p）ppGpp 通过依赖于无机多磷酸盐和 Lon 蛋白酶的调节级联激活毒素-抗毒素基因座来触发缓慢生长。
