Growth-rate dependent global effects on gene expression in bacteria

By Stefan Klumpp, Zhongge Zhang, Terence Hwa. Cell, 2009

726 citations recorded by the source corpus.

Summary Bacterial gene expression depends not only on specific regulations but also directly on bacterial growth, because important global parameters such as the abundance of RNA polymerases and ribosomes are all growth-rate dependent. Understanding these global effects is necessary for a quantitative understanding of gene regulation and for the robust design of synthetic genetic circuits. The observed growth-rate dependence of constitutive gene expression can be explained by a simple model using the measured growth-rate dependence of the relevant cellular parameters. More complex growth dependences for genetic circuits involving activators, repressors and feedback control were analyzed, and salient features were verified experimentally using synthetic circuits. The results suggest a novel feedback mechanism mediated by general growth-dependent effects and not requiring explicit gene regulation, if the expressed protein affects cell growth. This mechanism can lead to growth bistability and promote the acquisition of important physiological functions such as antibiotic resistance and tolerance (persistence).

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/362899a3dfd33a7b9152f11bbd7d9b2a2783e7a3

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Citations in the corpus

Cellular Decision-Making and Biological Noise: From Microbes to Mammals (2011, background): “Third, the landscape is not rigid: cells themselves may reshape the geography due to cell-cell interactions (Waters and Bassler, 2005) and the growth rate dependence of protein concentrations (Klumpp et al., 2009; Tan et al., 2009).”
Genome-scale models of metabolism and gene expression extend and refine growth phenotype prediction (2013, background): “For example, constitutively expressed genes display growth rate-dependent expression trends (Klumpp and Hwa, 2008; Klumpp et al, 2009), which might provide the cell with an economical way of responding to global changes in metabolic efficiency (Valgepea et al, 2013).”
A mechanistic link between cellular trade-offs, gene expression and growth (2015, neutral): “Denoting these proteins by q, we assume their transcription to be negatively auto-regulated to maintain stable levels across different growth conditions [1, 2]: ωq(a) = wqa θq+a × 1 1+(q/Kq) hq .”