Stability of bacterial toggle switches is enhanced by cell-cycle lengthening by several orders of magnitude

Joanna Jaruszewicz, Marek Kimmel, and Tomasz Lipniacki
Phys. Rev. E 89, 022710 – Published 11 February 2014

Abstract

Bistable regulatory elements are important for nongenetic inheritance, increase of cell-to-cell heterogeneity allowing adaptation, and robust responses at the population level. Here, we study computationally the bistable genetic toggle switch—a small regulatory network consisting of a pair of mutual repressors—in growing and dividing bacteria. We show that as cells with an inhibited growth exhibit high stability of toggle states, cell growth and divisions lead to a dramatic increase of toggling rates. The toggling rates were found to increase with rate of cell growth, and can be up to six orders of magnitude larger for fast growing cells than for cells with the inhibited growth. The effect is caused mainly by the increase of protein and mRNA burst sizes associated with the faster growth. The observation that fast growth dramatically destabilizes toggle states implies that rapidly growing cells may vigorously explore the epigenetic landscape enabling nongenetic evolution, while cells with inhibited growth adhere to the local optima. This can be a clever population strategy that allows the slow growing (but stress resistant) cells to survive long periods of unfavorable conditions. Simultaneously, at favorable conditions, this stress resistant (but slowly growing—or not growing) subpopulation may be replenished due to a high switching rate from the fast growing population.

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  • Received 27 October 2013
  • Revised 14 January 2014

DOI:https://doi.org/10.1103/PhysRevE.89.022710

©2014 American Physical Society

Authors & Affiliations

Joanna Jaruszewicz1, Marek Kimmel2,3, and Tomasz Lipniacki1,4,*

  • 1Institute of Fundamental Technological Research, Polish Academy of Sciences, 02-106 Warsaw, Poland
  • 2Departments of Statistics and Bioengineering, Rice University, Houston, Texas 77005, USA
  • 3Systems Engineering Group, Silesian University of Technology, 44-100 Gliwice, Poland
  • 4Department of Statistics, Rice University, Houston, Texas 77005, USA

  • *tlipnia@ippt.pan.pl

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Vol. 89, Iss. 2 — February 2014

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