The diffusive influx and carrier efflux have a strong effect on the bistability of the lac operon in Escherichia coli
The diffusive influx and carrier efflux have a strong effect on the bistability of the lac operon in Escherichia coli
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DOI：
10.1016/j.jtbi.2008.09.003
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发表时间：
2009-01-07
影响因子：
2
通讯作者：
Narang, Atul
中科院分区：
文献类型：
--
作者：
Noel, Jason T.;Pilyugin, Sergei S.;Narang, Atul
在无端诱导剂的存在下，大肠杆菌的lac操纵子表现出双稳定性。文献中的大多数模型假设诱导剂通过载体（渗透酶）进入细胞，并以扩散样过程退出。忽略了扩散内流和载流子外流。然而，对数据的分析表明，在非诱导细胞中，弥漫性内流与载体内流相当，在诱导细胞中，载体外流与弥漫性外流相当。由于双稳态意味着非诱导细胞和诱导细胞的稳态共存，因此这两种通量都不能忽略。我们提出了一个考虑这两种通量的模型，并表明：(1)阈值（即转录开启或关闭的细胞外诱导剂水平）受到这两种通量的深刻影响。弥漫性内流降低了开启阈值，消除了不可逆双稳态，这是一种与数据不一致的现象。载流子外排增加了关闭阈值，并在大渗透酶活性下消除了双稳定性，这一结论可以通过实验来验证。(2)通过考虑两种极限情况（无载流子外溢和无扩散内流）得到的简单解析表达式可以很好地逼近阈值。(3)模拟结果与异丙基硫代半乳糖苷（IPTG）的数据吻合较好，但与硫甲基半乳糖苷（TMG）的数据存在一定差异。我们讨论了差异的潜在来源。(C) 2008 Elsevier Ltd版权所有。
In the presence of gratuitous inducers, the lac operon of Escherichia coli exhibits bistability. Most models in the literature assume that the inducer enters the cell via the carrier (permease), and exits by a diffusion-like process. The diffusive influx and carrier efflux are neglected. However, analysis of the data shows that in non-induced cells, the diffusive influx is comparable to the carrier influx, and in induced cells, the carrier efflux is comparable to the diffusive efflux. Since bistability entails the coexistence of steady states corresponding to both non-induced and induced cells, neither one of these fluxes can be ignored. We present a model accounting for both fluxes, and show that: (1) The thresholds (i.e., the extracellular inducer levels at which transcription turns on or off) are profoundly affected by both fluxes. The diffusive influx reduces the on threshold, and eliminates irreversible bistability, a phenomenon that is inconsistent with data. The carrier efflux increases the off threshold, and abolishes bistability at large permease activities, a conclusion that can be tested experimentally. (2) The thresholds are well approximated by simple analytical expressions obtained by considering two limiting cases (no carrier efflux and no diffusive influx). (3) The simulations are in good agreement with the data for isopropyl thiogalactoside (IPTG), but somewhat discrepant with respect to the data for thiomethyl galactoside (TMG). We discuss the potential sources of the discrepancy. (C) 2008 Elsevier Ltd. All rights reserved.