Growth feedback as a basis for persister bistability
Growth feedback as a basis for persister bistability
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DOI：
10.1073/pnas.1320396110
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发表时间：
2014-01-07
影响因子：
11.1
通讯作者：
Levine, Herbert
中科院分区：
文献类型：
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作者：
Feng, Jingchen;Kessler, David A.;Levine, Herbert
在许多细菌群体中，有一小部分细胞被称为持久菌，与大多数细胞相比，它们对抗生素治疗的敏感性要低得多。坚持者处于休眠的新陈代谢状态，即使在基因上与活跃生长的细胞保持相同。细菌中的毒素和抗毒素模块被认为是持久存在的一个可能原因。HipBA是一个双基因操纵子，是大肠杆菌中许多染色体编码的毒素和抗毒素模块之一，HipA7等位基因突变是第一个被证实的高持久性突变体。在这里，我们提出了一个随机模型，它可以通过游离HipA与细胞生长速率的倒数耦合来产生HipBA系统的双稳态。活跃生长状态和休眠状态分别对应于该模型的稳定状态。波动可以实现从一种到另一种的过渡。该模型与合成启动子结构的实验数据完全一致。
A small fraction of cells in many bacterial populations, called persisters, are much less sensitive to antibiotic treatment than the majority. Persisters are in a dormant metabolic state, even while remaining genetically identical to the actively growing cells. Toxin and antitoxin modules in bacteria are believed to be one possible cause of persistence. A two-gene operon, HipBA, is one of many chromosomally encoded toxin and antitoxin modules in Escherichia coli and the HipA7 allelic variant was the first validated high-persistence mutant. Here, we present a stochastic model that can generate bistability of the HipBA system, via the reciprocal coupling of free HipA to the cellular growth rate. The actively growing state and the dormant state each correspond to a stable state of this model. Fluctuations enable transitions from one to the other. This model is fully in agreement with experimental data obtained with synthetic promoter constructs.