A broadly distributed toxin family mediates contact-dependent antagonism between gram-positive bacteria

  1. John C Whitney
  2. S Brook Peterson
  3. Jungyun Kim
  4. Manuel Pazos
  5. Adrian J Verster
  6. Matthew C Radey
  7. Hemantha D Kulasekara
  8. Mary Q Ching
  9. Nathan P Bullen
  10. Diane Bryant
  11. Young Ah Goo
  12. Michael G Surette
  13. Elhanan Borenstein
  14. Waldemar Vollmer
  15. Joseph D Mougous  Is a corresponding author
  1. McMaster University, Canada
  2. University of Washington, United States
  3. Newcastle University, United Kingdom
  4. Advanced Light Source, United States
  5. Northwestern University, United States

Abstract

The Firmicutes are a phylum of bacteria that dominate numerous polymicrobial habitats of importance to human health and industry. Although these communities are often densely colonized, a broadly distributed contact-dependent mechanism of interbacterial antagonism utilized by Firmicutes has not been elucidated. Here we show that proteins belonging to the LXG polymorphic toxin family present in Streptococus intermedius mediate cell contact- and Esx secretion pathway-dependent growth inhibition of diverse Firmicute species. The structure of one such toxin revealed a previously unobserved protein fold that we demonstrate directs the degradation of a uniquely bacterial molecule required for cell wall biosynthesis, lipid II. Consistent with our functional data linking LXG toxins to interbacterial interactions in S. intermedius, we show that LXG genes are prevalent in the human gut microbiome, a polymicrobial community dominated by Firmicutes. We speculate that interbacterial antagonism mediated by LXG toxins plays a critical role in shaping Firmicute-rich bacterial communities.

Article and author information

Author details

  1. John C Whitney

    Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. S Brook Peterson

    Department of Microbiology, School of Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jungyun Kim

    Department of Microbiology, School of Medicine, 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:" 0000-0003-3793-4264
  4. Manuel Pazos

    Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Adrian J Verster

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

    Department of Microbiology, School of Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Hemantha D Kulasekara

    Department of Microbiology, School of Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Mary Q Ching

    Department of Microbiology, School of Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Nathan P Bullen

    Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Diane Bryant

    Experimental Systems Group, Advanced Light Source, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Young Ah Goo

    Northwestern Proteomics Core Facility, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Michael G Surette

    Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  13. Elhanan Borenstein

    Department of Genome Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Waldemar Vollmer

    Centre for Bacterial Cell Biology, Newcastle University, Newcastle, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. 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

Canadian Institutes of Health Research

  • John C Whitney

Natural Sciences and Engineering Research Council of Canada

  • Adrian J Verster

Wellcome (101824/Z/13/Z)

  • Waldemar Vollmer

National Cancer Institute (CCSG P30 CA060553)

  • Young Ah Goo

National Institutes of Health (AI080609)

  • Joseph D Mougous

Howard Hughes Medical Institute

  • Joseph D Mougous

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

Reviewing Editor

  1. Michael T Laub, Massachusetts Institute of Technology, United States

Publication history

  1. Received: March 20, 2017
  2. Accepted: July 10, 2017
  3. Accepted Manuscript published: July 11, 2017 (version 1)
  4. Accepted Manuscript updated: July 12, 2017 (version 2)
  5. Version of Record published: August 14, 2017 (version 3)
  6. Version of Record updated: August 24, 2017 (version 4)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. John C Whitney
  2. S Brook Peterson
  3. Jungyun Kim
  4. Manuel Pazos
  5. Adrian J Verster
  6. Matthew C Radey
  7. Hemantha D Kulasekara
  8. Mary Q Ching
  9. Nathan P Bullen
  10. Diane Bryant
  11. Young Ah Goo
  12. Michael G Surette
  13. Elhanan Borenstein
  14. Waldemar Vollmer
  15. Joseph D Mougous
(2017)
A broadly distributed toxin family mediates contact-dependent antagonism between gram-positive bacteria
eLife 6:e26938.
https://doi.org/10.7554/eLife.26938
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