Abstract

Bacterial survival is fraught with antagonism, including that deriving from viruses and competing bacterial cells. It is now appreciated that bacteria mount complex antiviral responses; however, whether a coordinated defense against bacterial threats is undertaken is not well understood. Previously we showed that Pseudomonas aeruginosa possess a danger sensing pathway that is a critical fitness determinant during competition against other bacteria. Here, we conducted genome-wide screens in P. aeruginosa that reveal three conserved and widespread interbacterial antagonism resistance clusters (arc1-3). We find that although arc1-3 are coordinately activated by the Gac/Rsm danger sensing system, they function independently and provide idiosyncratic defense capabilities, distinguishing them from general stress response pathways. Our findings demonstrate that Arc3 family proteins provide specific protection against phospholipase toxins by preventing the accumulation of lysophospholipids in a manner distinct from previously characterized membrane repair systems. These findings liken the response of P. aeruginosa to bacterial threats to that of eukaryotic innate immunity, wherein threat detection leads to the activation of specialized defense systems.

Data availability

Sequence data associated with this study is available from the Sequence Read Archive at BioProject PRJNA754428 (http://www.ncbi.nlm.nih.gov/bioproject/754428).

The following data sets were generated

Article and author information

Author details

  1. See-Yeun Ting

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

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

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Rutan Zhang

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

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

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

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Savannah K Bertolli

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Larry A Gallagher

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

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Kelsi M Penewit

    Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Stephen J. Salipante

    Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Libin Xu

    Department of Medicinal Chemistry, 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:" 0000-0003-1021-5200
  14. 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
  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

National Institutes of Health (AI080609)

  • Joseph D Mougous

National Institutes of Health (DK089507)

  • Stephen J. Salipante

National Institutes of Health (R01AI136979)

  • Libin Xu

Cystic Fibrosis Foundation (SINGH19R0)

  • Stephen J. Salipante

National Institutes of Health (S10OD026741)

  • Stephen J. Salipante

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. Tâm Mignot, CNRS-Aix Marseille University, France

Version history

  1. Preprint posted: August 23, 2021 (view preprint)
  2. Received: October 12, 2021
  3. Accepted: February 16, 2022
  4. Accepted Manuscript published: February 17, 2022 (version 1)
  5. Version of Record published: March 16, 2022 (version 2)

Copyright

© 2022, Ting 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.

Metrics

  • 2,352
    views
  • 354
    downloads
  • 6
    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. See-Yeun Ting
  2. Kaitlyn D LaCourse
  3. Hannah E Ledvina
  4. Rutan Zhang
  5. Matthew C Radey
  6. Hemantha D Kulasekara
  7. Rahul Somavanshi
  8. Savannah K Bertolli
  9. Larry A Gallagher
  10. Jennifer Kim
  11. Kelsi M Penewit
  12. Stephen J. Salipante
  13. Libin Xu
  14. S Brook Peterson
  15. Joseph D Mougous
(2022)
Discovery of coordinately regulated pathways that provide innate protection against interbacterial antagonism
eLife 11:e74658.
https://doi.org/10.7554/eLife.74658

Share this article

https://doi.org/10.7554/eLife.74658

Further reading

    1. Microbiology and Infectious Disease
    Swagata Bose, Satya Ranjan Sahu ... Narottam Acharya
    Research Article

    Despite current antifungal therapy, invasive candidiasis causes >40% mortality in immunocompromised individuals. Therefore, developing an antifungal vaccine is a priority. Here, we could for the first time successfully attenuate the virulence of Candida albicans by treating it with a fungistatic dosage of EDTA and demonstrate it to be a potential live whole cell vaccine by using murine models of systemic candidiasis. EDTA inhibited the growth and biofilm formation of C. albicans. RNA-seq analyses of EDTA-treated cells (CAET) revealed that genes mostly involved in metal homeostasis and ribosome biogenesis were up- and down-regulated, respectively. Consequently, a bulky cell wall with elevated levels of mannan and β-glucan, and reduced levels of total monosomes and polysomes were observed. CAET was eliminated faster than the untreated strain (Ca) as found by differential fungal burden in the vital organs of the mice. Higher monocytes, granulocytes, and platelet counts were detected in Ca- vs CAET-challenged mice. While hyper-inflammation and immunosuppression caused the killing of Ca-challenged mice, a critical balance of pro- and anti-inflammatory cytokines-mediated immune responses are the likely reasons for the protective immunity in CAET-infected mice.

    1. Microbiology and Infectious Disease
    Tomoko Kubori, Kohei Arasaki ... Hiroki Nagai
    Research Article

    Rab GTPases are representative targets of manipulation by intracellular bacterial pathogens for hijacking membrane trafficking. Legionella pneumophila recruits many Rab GTPases to its vacuole and exploits their activities. Here, we found that infection-associated regulation of Rab10 dynamics involves ubiquitin signaling cascades mediated by the SidE and SidC families of Legionella ubiquitin ligases. Phosphoribosyl-ubiquitination of Rab10 catalyzed by the SidE ligases is crucial for its recruitment to the bacterial vacuole. SdcB, the previously uncharacterized SidC-family effector, resides on the vacuole and contributes to retention of Rab10 at the late stages of infection. We further identified MavC as a negative regulator of SdcB. By the transglutaminase activity, MavC crosslinks ubiquitin to SdcB and suppresses its function, resulting in elimination of Rab10 from the vacuole. These results demonstrate that the orchestrated actions of many L. pneumophila effectors fine-tune the dynamics of Rab10 during infection.