1. Microbiology and Infectious Disease

Metabolic basis for the evolution of a common pathogenic Pseudomonas aeruginosa variant

  1. Dallas L Mould
  2. Mirjana Stevanovic
  3. Alix Ashare
  4. Daniel Schultz
  5. Deborah A Hogan  Is a corresponding author
  1. Geisel School of Medicine at Dartmouth, United States
  2. Dartmouth-Hitchock Medical Center, United States
https://doi.org/10.7554/eLife.76555
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Cite this article
  1. Dallas L Mould
  2. Mirjana Stevanovic
  3. Alix Ashare
  4. Daniel Schultz
  5. Deborah A Hogan
(2022)
Metabolic basis for the evolution of a common pathogenic Pseudomonas aeruginosa variant
eLife 11:e76555.
https://doi.org/10.7554/eLife.76555
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Abstract

Microbes frequently evolve in reproducible ways. Here, we show that differences in specific metabolic regulation rather than inter-strain interactions explain the frequent presence of lasR loss-of-function mutations in the bacterial pathogen Pseudomonas aeruginosa. While LasR contributes to virulence through its role in quorum sensing, lasR mutants have been associated with more severe disease. A model based on the intrinsic growth kinetics for a wild type strain and its LasR- derivative, in combination with an experimental evolution based genetic screen and further genetics analyses, indicated that differences in metabolism were sufficient to explain the rise of these common mutant types. The evolution of LasR- lineages in laboratory and clinical isolates depended on activity of the two-component system CbrAB, which modulates substrate prioritization through the catabolite repression control pathway. LasR- lineages frequently arise in cystic fibrosis lung infections and their detection correlates with disease severity. Our analysis of bronchoalveolar lavage fluid metabolomes identified compounds that negatively correlate with lung function, and we show that these compounds support enhanced growth of LasR- cells in a CbrB-controlled manner. We propose that in vivo metabolomes contribute to pathogen evolution, which may influence the progression of disease and its treatment.

Data availability

All sequencing data is available on the Sequence Read Archive with accession number PRJNA786588 upon publication. All data generated or analyzed and all code used during this study are included in the manuscript or associated files.

The following data sets were generated

Article and author information

Author details

  1. Dallas L Mould

    Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Mirjana Stevanovic

    Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Alix Ashare

    Department of Medicine, Dartmouth-Hitchock Medical Center, Lebanon, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Daniel Schultz

    Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Deborah A Hogan

    Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, United States
    For correspondence
    dhogan@dartmouth.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6366-2971

Funding

Cystic Fibrosis Foundation (HOGAN19G0)

  • Dallas L Mould
  • Deborah A Hogan

Cystic Fibrosis Foundation (ASHARE20P0)

  • Alix Ashare

Cystic Fibrosis Foundation (STANTO19R0)

  • Daniel Schultz

Cystic Fibrosis Foundation (T32AI007519)

  • Dallas L Mould

National Institutes of Health (R01HL122372)

  • Alix Ashare

National Institutes of Health (GM130454)

  • Mirjana Stevanovic
  • Daniel Schultz

National Institutes of Health (P20GM113132)

  • Dallas L Mould
  • Deborah A Hogan

National Institutes of Health (DK117469)

  • Dallas L Mould
  • Alix Ashare
  • Daniel Schultz
  • Deborah A Hogan

National Institutes of Health (P30CA023108)

  • Dallas L Mould
  • Alix Ashare
  • Daniel Schultz
  • Deborah A Hogan

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

Reviewing Editor

  1. Vaughn S Cooper, University of Pittsburgh, United States

Publication history

  1. Received: December 21, 2021
  2. Preprint posted: January 14, 2022 (view preprint)
  3. Accepted: April 24, 2022
  4. Accepted Manuscript published: May 3, 2022 (version 1)
  5. Version of Record published: June 23, 2022 (version 2)

Copyright

© 2022, Mould 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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  1. Dallas L Mould
  2. Mirjana Stevanovic
  3. Alix Ashare
  4. Daniel Schultz
  5. Deborah A Hogan
(2022)
Metabolic basis for the evolution of a common pathogenic Pseudomonas aeruginosa variant
eLife 11:e76555.
https://doi.org/10.7554/eLife.76555

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