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Reduction of translating ribosomes enables Escherichia coli to maintain elongation rates during slow growth

Nature Microbiology volume 2, Article number: 16231 (2017) Cite this article

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Abstract

Bacteria growing under different conditions experience a broad range of demand on the rate of protein synthesis, which profoundly affects cellular resource allocation. During fast growth, protein synthesis has long been known to be modulated by adjusting the ribosome content, with the vast majority of ribosomes engaged at a near-maximal rate of elongation. Here, we systematically characterize protein synthesis by Escherichia coli, focusing on slow-growth conditions. We establish that the translational elongation rate decreases as growth slows, exhibiting a Michaelis–Menten dependence on the abundance of the cellular translational apparatus. However, an appreciable elongation rate is maintained even towards zero growth, including the stationary phase. This maintenance, critical for timely protein synthesis in harsh environments, is accompanied by a drastic reduction in the fraction of active ribosomes. Interestingly, well-known antibiotics such as chloramphenicol also cause a substantial reduction in the pool of active ribosomes, instead of slowing down translational elongation as commonly thought.

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Figure 1: Characteristics of protein synthesis capacity under nutrient limitation.
Figure 2: Characteristics of protein synthesis capacity under translation limitation by Cm inhibition.
Figure 3: Growth-rate dependence of the active ribosome fraction.
Figure 4: Models for the reduction of the active ribosome fraction at slow growth.

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  • 14 July 2017

    In the PDF version of this article previously published, the year of publication provided in the footer of each page and in the 'How to cite' section was erroneously given as 2017, it should have been 2016. This error has now been corrected. The HTML version of the article was not affected.

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Acknowledgements

The authors are grateful for discussions with numerous colleagues including Z. Ignatova, S. Klumpp, S. Pedersen, S. Schink, J. Silverman, M. Scott, R. Young and members of the Hwa laboratory at various stages of this work. This research is supported by NIH grant R01GM109069 (to T.H.) and grant 31530081 of the National Natural Science Fund of the People's Republic of China (NSFC; to Y.P.W.). K.F. acknowledges support from NIH grant R01GM072528. J.R.W. acknowledges NIH grant GM118850. M.Z. acknowledges financial support from the China Scholarship Council (CSC; 201306010039).

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Author notes

  1. Xiongfeng Dai and Manlu Zhu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Physics, University of California at San Diego, La Jolla, 92093-0374, California, USA

    Xiongfeng Dai, Manlu Zhu, Mya Warren, Rohan Balakrishnan, Hiroyuki Okano & Terence Hwa

  2. State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, 100871, China

    Xiongfeng Dai, Manlu Zhu & Yi-Ping Wang

  3. Department of Microbiology and Ohio State Biochemistry Program, The Ohio State University, Columbus, 43210, Ohio, USA

    Rohan Balakrishnan & Kurt Fredrick

  4. Department of Integrative Structural and Computational Biology, Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, 92037, California, USA

    Vadim Patsalo & James R. Williamson

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  1. Xiongfeng Dai
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Contributions

X.D., M.Z., M.W. and T.H. designed the study. X.D., M.Z., R.B. and V.P. performed experiments. X.D., M.Z., M.W., H.O., V.P., J.R.W., K.F., Y.-P.W. and T.H. analysed the data. X.D., M.Z., M.W., Y.-P.W. and T.H. wrote the paper and the Supplementary Information.

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Correspondence to Yi-Ping Wang or Terence Hwa.

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Supplementary information

Supplementary information

Supplementary Notes 1–5, Supplementary Tables 1–12, Supplementary Figures 1–20, Supplementary References (PDF 4670 kb)

Supplementary Table 9

Proteome abundances of individual r-proteins under nutrient limitation and Cm inhibition. (XLSX 48 kb)

Supplementary Table 10

Proteome abundance of individual r-proteins of the reference condition. (XLSX 64 kb)

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Dai, X., Zhu, M., Warren, M. et al. Reduction of translating ribosomes enables Escherichia coli to maintain elongation rates during slow growth. Nat Microbiol 2, 16231 (2017). https://doi.org/10.1038/nmicrobiol.2016.231

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