Bacterial sugar utilization gives rise to distinct single-cell behaviours.

Bacterial sugar utilization gives rise to distinct single-cell behaviours.
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DOI:
10.1111/mmi.12695
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发表时间:
2014-09
影响因子:
3.6
通讯作者:
Beisel CL
Beisel CL
中科院分区:
生物学2区
文献类型:
--
作者:
Afroz T;Biliouris K;Kaznessis Y;Beisel CL

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诱导利用途径反映了微生物从环境中摄取和消耗糖的广泛策略。尽管它们具有广泛的重要性和广泛的特征,但人们对这些途径在单个细胞中如何自然地对它们的诱导糖作出反应知之甚少。在这里,我们进行了单细胞分析,以探索模式细菌大肠杆菌中代表性途径的行为。我们观察到不同的单细胞行为,包括统一的反应(d -乳糖、d -半乳糖、n -乙酰氨基葡萄糖、n -乙酰神经氨酸),“全或无”的反应(d -木糖、l-鼠李糖),以及它们的复杂组合(l-阿拉伯糖、d -葡萄糖酸盐)。对转基因途径的数学建模和探索表明,这些途径背后的简单框架——诱导转运和诱导分解代谢——可能导致大多数这些行为。糖分解代谢也是一个重要的特征,因为分解代谢的破坏消除了可调节的诱导,并增强了对先前条件的记忆。例如,即使在没有外源糖的情况下,对内源性合成糖反应的途径中分解代谢的破坏也会导致全途径诱导。我们的研究结果证明了这种简单的生物学框架的显著灵活性,对环境适应和合成利用途径的工程作为可滴定表达系统和代谢工程具有直接意义。
Inducible utilization pathways reflect widespread microbial strategies to uptake and consume sugars from the environment. Despite their broad importance and extensive characterization, little is known how these pathways naturally respond to their inducing sugar in individual cells. Here, we performed single-cell analyses to probe the behavior of representative pathways in the model bacterium Escherichia coli. We observed diverse single-cell behaviors, including uniform responses (D-lactose, D-galactose, N-acetylglucosamine, N-acetylneuraminic acid), “all-or-none” responses (D-xylose, L-rhamnose), and complex combinations thereof (L-arabinose, D-gluconate). Mathematical modeling and probing of genetically modified pathways revealed that the simple framework underlying these pathways—inducible transport and inducible catabolism—could give rise to most of these behaviors. Sugar catabolism was also an important feature, as disruption of catabolism eliminated tunable induction as well as enhanced memory of previous conditions. For instance, disruption of catabolism in pathways that respond to endogenously synthesized sugars led to full pathway induction even in the absence of exogenous sugar. Our findings demonstrate the remarkable flexibility of this simple biological framework, with direct implications for environmental adaptation and the engineering of synthetic utilization pathways as titratable expression systems and for metabolic engineering.
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