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.

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

  • 2,689
    views
  • 382
    downloads
  • 10
    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. Immunology and Inflammation
    2. Microbiology and Infectious Disease
    Axelle Amen, Randy Yoo ... Matthijs M Jore
    Research Article

    Circulating sexual stages of Plasmodium falciparum (Pf) can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies can efficiently block parasite transmission. In search for naturally acquired antibodies targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages of Pf in the form of gametes and gametocyte extracts. We isolated mAbs reactive against a range of Pf proteins including well-established targets Pfs48/45 and Pfs230. One mAb, B1E11K, was cross-reactive to various proteins containing glutamate-rich repetitive elements expressed at different stages of the parasite life cycle. A crystal structure of two B1E11K Fab domains in complex with its main antigen, RESA, expressed on asexual blood stages, showed binding of B1E11K to a repeating epitope motif in a head-to-head conformation engaging in affinity-matured homotypic interactions. Thus, this mode of recognition of Pf proteins, previously described only for Pf circumsporozoite protein (PfCSP), extends to other repeats expressed across various stages. The findings augment our understanding of immune-pathogen interactions to repeating elements of the Plasmodium parasite proteome and underscore the potential of the novel mAb identification method used to provide new insights into the natural humoral immune response against Pf.

    1. Microbiology and Infectious Disease
    Nicolas Flaugnatti, Loriane Bader ... Melanie Blokesch
    Research Article Updated

    The type VI secretion system (T6SS) is a sophisticated, contact-dependent nanomachine involved in interbacterial competition. To function effectively, the T6SS must penetrate the membranes of both attacker and target bacteria. Structures associated with the cell envelope, like polysaccharides chains, can therefore introduce spatial separation and steric hindrance, potentially affecting the efficacy of the T6SS. In this study, we examined how the capsular polysaccharide (CPS) of Acinetobacter baumannii affects T6SS’s antibacterial function. Our findings show that the CPS confers resistance against T6SS-mediated assaults from rival bacteria. Notably, under typical growth conditions, the presence of the surface-bound capsule also reduces the efficacy of the bacterium’s own T6SS. This T6SS impairment is further enhanced when CPS is overproduced due to genetic modifications or antibiotic treatment. Furthermore, we demonstrate that the bacterium adjusts the level of the T6SS inner tube protein Hcp according to its secretion capacity, by initiating a degradation process involving the ClpXP protease. Collectively, our findings contribute to a better understanding of the dynamic relationship between T6SS and CPS and how they respond swiftly to environmental challenges.