细菌中生长速率依赖性的全局基因表达变化。

Growth rate-dependent global effects on gene expression in bacteria.

机构信息

Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, CA 92093-0374, USA.

出版信息

Cell. 2009 Dec 24;139(7):1366-75. doi: 10.1016/j.cell.2009.12.001.

Abstract

Bacterial gene expression depends not only on specific regulatory mechanisms, but also on bacterial growth, because important global parameters such as the abundance of RNA polymerases and ribosomes are all growth-rate dependent. Understanding of these global effects is necessary for a quantitative understanding of gene regulation and for the design of synthetic genetic circuits. We find that the observed growth-rate dependence of constitutive gene expression can be explained by a simple model using the measured growth-rate dependence of the relevant cellular parameters. More complex growth dependencies for genetic circuits involving activators, repressors, and feedback control were analyzed and verified experimentally with synthetic circuits. Additional results suggest a feedback mechanism mediated by general growth-dependent effects that does not require explicit gene regulation if the expressed protein affects cell growth. This mechanism can lead to growth bistability and promote the acquisition of important physiological functions such as antibiotic resistance and tolerance (persistence).

摘要

细菌基因表达不仅取决于特定的调控机制,还取决于细菌的生长,因为 RNA 聚合酶和核糖体等重要的全局参数的丰度都依赖于生长速率。为了定量理解基因调控并设计合成遗传回路,需要了解这些全局效应。我们发现,通过使用相关细胞参数的测量生长速率依赖性,使用一个简单的模型可以解释所观察到的组成型基因表达的生长速率依赖性。对于涉及激活子、抑制剂和反馈控制的遗传回路的更复杂的生长依赖性,通过合成回路进行了分析和实验验证。其他结果表明,如果表达的蛋白质影响细胞生长,则存在一种由普遍的生长依赖性效应介导的反馈机制,而不需要明确的基因调控。这种机制可以导致生长双稳态,并促进获得重要的生理功能,如抗生素抗性和耐受性(持久性)。

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