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Cytosolic Crowding Drives the Dynamics of Both Genome and Cytosol in Escherichia coli Challenged with Sub-lethal Antibiotic Treatments
iScience ( IF 5.8 ) Pub Date : 2020-09-15 , DOI: 10.1016/j.isci.2020.101560
Michal Wlodarski 1, 2 , Leonardo Mancini 1 , Bianca Raciti 1 , Bianca Sclavi 3 , Marco Cosentino Lagomarsino 4 , Pietro Cicuta 5
Affiliation  

In contrast to their molecular mode of action, the system-level effect of antibiotics on cells is only beginning to be quantified. Molecular crowding is expected to be a relevant global regulator, which we explore here through the dynamic response phenotypes in Escherichia coli, at single-cell resolution, under sub-lethal regimes of different classes of clinically relevant antibiotics, acting at very different levels in the cell. We measure chromosomal mobility through tracking of fast (<15 s timescale) fluctuations of fluorescently tagged chromosomal loci, and we probe the fluidity of the cytoplasm by tracking cytosolic aggregates. Measuring cellular density, we show how the overall levels of macromolecular crowding affect both quantities, regardless of antibiotic-specific effects. The dominant trend is a strong correlation between the effects in different parts of the chromosome and between the chromosome and cytosol, supporting the concept of an overall global role of molecular crowding in cellular physiology.



中文翻译:

细胞质拥挤驱动了接受亚致死抗生素治疗的大肠杆菌中基因组和细胞质的动态

与它们的分子作用模式相反,抗生素对细胞的系统水平影响才刚刚开始被量化。分子拥挤预计将成为一个相关的全局调节因子,我们在这里通过大肠杆菌的动态反应表型进行探索,在单细胞分辨率下,在不同类别的临床相关抗生素的亚致死制度下,在不同的水平上发挥作用细胞。我们通过跟踪荧光标记染色体位点的快速(<15 秒时间尺度)波动来测量染色体流动性,并通过跟踪胞质聚集体来探测细胞质的流动性。通过测量细胞密度,我们展示了大分子拥挤的总体水平如何影响这两个数量,而不管抗生素的特异性作用如何。主要趋势是染色体不同部分以及染色体和细胞质之间的影响之间存在很强的相关性,支持分子拥挤在细胞生理学中的整体全局作用的概念。

更新日期:2020-09-25
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