Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Department of Civil, Environmental and Geomatic Engineering, Institute of Environmental Engineering, ETH Zurich, Zurich, Switzerland.
Mol Syst Biol. 2018 Nov 5;14(11):e8623. doi: 10.15252/msb.20188623.
In natural environments, microbes are typically non-dividing and gauge when nutrients permit division. Current models are phenomenological and specific to nutrient-rich, exponentially growing cells, thus cannot predict the first division under limiting nutrient availability. To assess this regime, we supplied starving with glucose pulses at increasing frequencies. Real-time metabolomics and microfluidic single-cell microscopy revealed unexpected, rapid protein, and nucleic acid synthesis already from minuscule glucose pulses in non-dividing cells. Additionally, the lag time to first division shortened as pulsing frequency increased. We pinpointed division timing and dependence on nutrient frequency to the changing abundance of the division protein FtsZ. A dynamic, mechanistic model quantitatively relates lag time to FtsZ synthesis from nutrient pulses and FtsZ protease-dependent degradation. Lag time changed in model-congruent manners, when we experimentally modulated the synthesis or degradation of FtsZ. Thus, limiting abundance of FtsZ can quantitatively predict timing of the first cell division.
在自然环境中,微生物通常是非分裂的,并且只有在营养物质允许分裂时才会进行分裂。目前的模型是现象学的,并且特定于营养丰富、呈指数增长的细胞,因此无法预测在有限的营养供应下的第一次分裂。为了评估这种状态,我们以递增的频率向饥饿的细胞提供葡萄糖脉冲。实时代谢组学和微流控单细胞显微镜技术揭示了意想不到的快速蛋白质和核酸合成,即使在非分裂细胞中,葡萄糖脉冲也非常微小。此外,随着脉冲频率的增加,第一次分裂的滞后时间缩短。我们将细胞分裂的时间和对营养频率的依赖性确定为分裂蛋白 FtsZ 的变化丰度。一个动态的、机械的模型定量地将滞后时间与营养脉冲中的 FtsZ 合成以及 FtsZ 蛋白酶依赖性降解联系起来。当我们通过实验调节 FtsZ 的合成或降解时,滞后时间会以与模型一致的方式发生变化。因此,FtsZ 的有限丰度可以定量预测第一次细胞分裂的时间。