Carbon catabolite repression correlates with the maintenance of near invariant molecular crowding in proliferating E. coli cells

BMC Systems Biology

Zoltán N Oltvai¹  Ziv Bar-Joseph³  Katsuhiko Warita¹  Tomoko Warita¹  Aaron Wise⁴  Alexei Vazquez²  Yi Zhou¹ 

[1] Department of Pathology, University of Pittsburgh, School of Medicine, S701 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15213, USA;Department of Radiation Oncology and Center for Systems Biology, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA;Machine Learning Department, Carnegie Mellon University, Pittsburgh, PA 15217, USA;Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, PA 15217, USA

关键词: Growth rate;    Macromolecular crowding (MC);    Carbon catabolite repression (CCR);    Metabolic network;   

Others  :  1141705
DOI  :  10.1186/1752-0509-7-138

 received in 2013-06-06, accepted in 2013-12-05,  发布年份 2013

【 摘 要 】

Background

Carbon catabolite repression (CCR) is critical for optimal bacterial growth, and in bacterial (and yeast) cells it leads to their selective consumption of a single substrate from a complex environment. However, the root cause(s) for the development of this regulatory mechanism is unknown. Previously, a flux balance model (FBAwMC) of Escherichia coli metabolism that takes into account the crowded intracellular milieu of the bacterial cell correctly predicted selective glucose uptake in a medium containing five different carbon sources, suggesting that CCR may be an adaptive mechanism that ensures optimal bacterial metabolic network activity for growth.

Results

Here, we show that slowly growing E. coli cells do not display CCR in a mixed substrate culture and gradual activation of CCR correlates with an increasing rate of E. coli cell growth and proliferation. In contrast, CCR mutant cells do not achieve fast growth in mixed substrate culture, and display differences in their cell volume and density compared to wild-type cells. Analyses of transcriptome data from wt E. coli cells indicate the expected regulation of substrate uptake and metabolic pathway utilization upon growth rate change. We also find that forced transient increase of intracellular crowding or transient perturbation of CCR delay cell growth, the latter leading to associated cell density-and volume alterations.

Conclusions

CCR is activated at an increased bacterial cell growth rate when it is required for optimal cell growth while intracellular macromolecular density is maintained within a narrow physiological range. In addition to CCR, there are likely to be other regulatory mechanisms of cell metabolism that have evolved to ensure optimal cell growth in the context of the fundamental biophysical constraint imposed by intracellular molecular crowding.

【 授权许可】

   
2013 Zhou et al.; licensee BioMed Central Ltd.

【 图 表 】

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