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

Nature Microbiology volume 2, Article number: 16249 (2017) Cite this article

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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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Figure 1: Characterization of the yccE locus.
Figure 2: H-NS represses intragenic yccE transcription and associated fitness costs.
Figure 3: H-NS represses intragenic transcription and associated fitness costs at many loci.
Figure 4: Most transcription is uniformly downregulated in cells lacking H-NS.

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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.

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Author notes

  1. Gabriele Baniulyte & Richard P. Bonocora

    Present address: †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.).,

Authors and 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, 12208, New York, USA

    Anne M. Stringer, Richard P. Bonocora & Joseph T. Wade

  3. Department of Physics, Biological Physics Research Group, Clarendon Laboratory, 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, 12201, New York, 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.

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Correspondence to David C. Grainger.

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Lamberte, L., Baniulyte, G., Singh, S. et al. Horizontally acquired AT-rich genes in Escherichia coli cause toxicity by sequestering RNA polymerase. Nat Microbiol 2, 16249 (2017). https://doi.org/10.1038/nmicrobiol.2016.249

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