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An interbacterial DNA deaminase toxin directly mutagenizes surviving target populations

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Cite this article as: eLife 2021;10:e62967 doi: 10.7554/eLife.62967

Abstract

When bacterial cells come in contact, antagonism mediated by the delivery of toxins frequently ensues. The potential for such encounters to have long-term beneficial consequences in recipient cells has not been investigated. Here we examined the effects of intoxication by DddA, a cytosine deaminase delivered via the type VI secretion system (T6SS) of Burkholderia cenocepacia. Despite its killing potential, we observed that several bacterial species resist DddA and instead accumulate mutations. These mutations can lead to the acquisition of antibiotic resistance, indicating that even in the absence of killing, interbacterial antagonism can have profound consequences on target populations. Investigation of additional toxins from the deaminase superfamily revealed that mutagenic activity is a common feature of these proteins, including a representative we show targets single-stranded DNA and displays a markedly divergent structure. Our findings suggest that a surprising consequence of antagonistic interactions between bacteria could be the promotion of adaptation via the action of directly mutagenic toxins.

Data availability

Diffraction data have been deposited in PDB under the accession code 7JTU.Sequencing data have been deposited at the NCBI Trace and Short-Read Archive (SRA) under BioProject accession ID PRJNA659516.

The following data sets were generated

Article and author information

Author details

  1. Marcos H de Moraes

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. FoSheng Hsu

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Dean Huang

    Department of Physics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1235-5699
  4. Dustin E Bosch

    Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jun Zeng

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Matthew C Radey

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Noah Simon

    Biostatistics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Hannah E Ledvina

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jacob P Frick

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Paul A Wiggins

    Department of Physics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. S Brook Peterson

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2648-0965
  12. Joseph D Mougous

    Department of Microbiology, University of Washington, Seattle, United States
    For correspondence
    mougous@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5417-4861

Funding

National Institutes of Health (GM128191)

  • Paul A Wiggins

National Institutes of Health (AI080609)

  • Joseph D Mougous

Howard Hughes Medical Institute

  • Joseph D Mougous

Cystic Fibrosis Foundation (DEMORA18F0)

  • Marcos H de Moraes

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Vaughn S Cooper, University of Pittsburgh, United States

Publication history

  1. Received: September 11, 2020
  2. Accepted: January 14, 2021
  3. Accepted Manuscript published: January 15, 2021 (version 1)
  4. Version of Record published: February 23, 2021 (version 2)

Copyright

© 2021, de Moraes et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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