1. Microbiology and Infectious Disease
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Density-dependent resistance protects Legionella pneumophila from its own antimicrobial metabolite, HGA

  1. Tera C Levin  Is a corresponding author
  2. Brian P Goldspiel
  3. Harmit S Malik
  1. Fred Hutchinson Cancer Research Center, United States
Research Article
  • Cited 2
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Cite this article as: eLife 2019;8:e46086 doi: 10.7554/eLife.46086

Abstract

To persist in microbial communities, the bacterial pathogen Legionella pneumophila must withstand competition from neighboring bacteria. Here, we find that L. pneumophila can antagonize the growth of other Legionella species using a secreted inhibitor: HGA (homogentisic acid). Unexpectedly, L. pneumophila can itself be inhibited by HGA secreted from neighboring, isogenic strains. Our genetic approaches further identify lpg1681 as a gene that modulates L. pneumophila susceptibility to HGA. We find that L. pneumophila sensitivity to HGA is density-dependent and cell intrinsic. This resistance is not mediated by the stringent response nor the previously described Legionella quorum-sensing pathway. Instead, L. pneumophila cells secrete HGA only when they are conditionally HGA-resistant, which allows these bacteria to produce a potentially self-toxic molecule while restricting the opportunity for self-harm. We propose that established Legionella communities may deploy molecules such as HGA as an unusual public good that can protect against invasion by low-density competitors.

Article and author information

Author details

  1. Tera C Levin

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    tlevin@fredhutch.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7883-8522
  2. Brian P Goldspiel

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Harmit S Malik

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6005-0016

Funding

National Institute of Allergy and Infectious Diseases (1 K99 AI139344-01)

  • Tera C Levin

Howard Hughes Medical Institute

  • Brian P Goldspiel
  • Harmit S Malik

Damon Runyon Cancer Research Foundation (DRG 2228-15)

  • Tera C Levin

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

Reviewing Editor

  1. Dianne K Newman, California Institute of Technology, United States

Publication history

  1. Received: February 14, 2019
  2. Accepted: May 16, 2019
  3. Accepted Manuscript published: May 28, 2019 (version 1)
  4. Version of Record published: June 28, 2019 (version 2)

Copyright

© 2019, Levin 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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