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.

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.

Metrics

  • 7,109
    views
  • 1,197
    downloads
  • 145
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.26938

Further reading

    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease
    Clara Bekirian, Isabel Valsecchi ... Thierry Fontaine
    Research Article

    The cell wall of human fungal pathogens plays critical roles as an architectural scaffold and as a target and modulator of the host immune response. Although the cell wall of the pathogenic yeast Candida albicans is intensively studied, one of the major fibrillar components in its cell wall, β-1,6-glucan, has been largely neglected. Here, we show that β-1,6-glucan is essential for bilayered cell wall organization, cell wall integrity, and filamentous growth. For the first time, we show that β-1,6-glucan production compensates the defect in mannan elongation in the outer layer of the cell wall. In addition, β-1,6-glucan dynamics are also coordinated by host environmental stimuli and stresses with wall remodeling, where the regulation of β-1,6-glucan structure and chain length is a crucial process. As we point out that β-1,6-glucan is exposed at the yeast surface and modulate immune response, β-1,6-glucan must be considered a key factor in host–pathogen interactions.

    1. Cell Biology
    2. Microbiology and Infectious Disease
    Erick E Arroyo-Pérez, John C Hook ... Simon Ringgaard
    Research Article

    The coordination of cell cycle progression and flagellar synthesis is a complex process in motile bacteria. In γ-proteobacteria, the localization of the flagellum to the cell pole is mediated by the SRP-type GTPase FlhF. However, the mechanism of action of FlhF, and its relationship with the cell pole landmark protein HubP remain unclear. In this study, we discovered a novel protein called FipA that is required for normal FlhF activity and function in polar flagellar synthesis. We demonstrated that membrane-localized FipA interacts with FlhF and is required for normal flagellar synthesis in Vibrio parahaemolyticus, Pseudomonas putida, and Shewanella putrefaciens, and it does so independently of the polar localization mediated by HubP. FipA exhibits a dynamic localization pattern and is present at the designated pole before flagellar synthesis begins, suggesting its role in licensing flagellar formation. This discovery provides insight into a new pathway for regulating flagellum synthesis and coordinating cellular organization in bacteria that rely on polar flagellation and FlhF-dependent localization.