Article

Horizontally acquired AT-rich genes in Escherichia coli cause toxicity by sequestering RNA polymerase

  • Nature Microbiology 2, Article number: 16249 (2017)
  • doi:10.1038/nmicrobiol.2016.249
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Abstract

Horizontal gene transfer permits rapid dissemination of genetic elements between individuals in bacterial populations. Transmitted DNA sequences may encode favourable traits. However, if the acquired DNA has an atypical base composition, it can reduce host fitness. Consequently, bacteria have evolved strategies to minimize the harmful effects of foreign genes. Most notably, xenogeneic silencing proteins bind incoming DNA that has a higher AT content than the host genome. An enduring question has been why such sequences are deleterious. Here, we showed that the toxicity of AT-rich DNA in Escherichia coli frequently results from constitutive transcription initiation within the coding regions of genes. Left unchecked, this causes titration of RNA polymerase and a global downshift in host gene expression. Accordingly, a mutation in RNA polymerase that diminished the impact of AT-rich DNA on host fitness reduced transcription from constitutive, but not activator-dependent, promoters.

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Acknowledgements

This work was funded by a Leverhulme Trust project grant (RPG-2013-147) and Wellcome Trust Career Development Fellowship (WT085092MA) awarded to D.C.G. Support for J.T.W. was a National Institutes of Health Director's New Innovator Award (1DP2OD007188). A.N.K. and M.S. were supported by a Biotechnology and Biological Sciences Research Council grant (BB/N018656/1, to A.N.K. and M.S.) and a Wellcome Trust Investigatorship (110164/Z/15/Z, to A.N.K.). We thank J. Hinton for the gift of anti-H-NS antiserum.

Author information

Author notes

    • Gabriele Baniulyte
    •  & Richard P. Bonocora

    Present address: Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, New York 12201, USA (G.B.); Department of Biological Sciences, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180-3590, USA (R.B.).

Affiliations

  1. Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK

    • Lisa E. Lamberte
    • , Gabriele Baniulyte
    • , Shivani S. Singh
    •  & David C. Grainger
  2. New York State Department of Health, Wadsworth Center, Albany, New York 12208, USA

    • Anne M. Stringer
    • , Richard P. Bonocora
    •  & Joseph T. Wade
  3. Biological Physics Research Group, Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK

    • Mathew Stracy
    •  & Achillefs N. Kapanidis
  4. Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, New York 12201, USA

    • Joseph T. Wade

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Contributions

D.C.G. and J.T.W. designed the study and wrote the manuscript. L.E.L., G.B., S.S.S., A.M.S., R.P.B. and M.S. generated the data and prepared it for publication. M.S. and A.N.K. provided new analytical tools and critically discussed the manuscript with D.C.G. and J.T.W. All authors contributed to data analysis and interpretation.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David C. Grainger.

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    Supplementary Figures 1–7, Supplementary Table 1.