Host genetic selection for cold tolerance shapes microbiome composition and modulates its response to temperature

  1. Fotini Kokou
  2. Goor Sasson
  3. Tali Nitzan
  4. Adi Doron-Faigenboim
  5. Sheenan Harpaz
  6. Avner Cnaani
  7. Itzhak Mizrahi  Is a corresponding author
  1. Ben-Gurion University of the Negev, Israel
  2. Agricultural Research Organization, Israel

Abstract

The hologenome concept proposes that microbes together with their hosting organism are an independent unit of selection. Motivated by this concept, we hypothesized that thermal acclimation in poikilothermic organisms is connected to their microbiome composition due to their inability to maintain their body temperature. To test this hypothesis, we used a unique experimental setup with a transgenerational selective breeding scheme for cold tolerance in tropical tilapias. We tested the effects of the selection on the gut microbiome and host transcriptomic response. Interestingly, we found that host genetic selection for thermal tolerance shapes microbiome composition and its response to cold. The microbiomes of cold-resistant fish showed higher resilience to temperature changes, indicating that the microbiome is shaped by its host's selection. These findings are consistent with the hologenome concept and highlight the connection between the host and its microbiome's response to the environment.

Data availability

Data has been deposited in the SRA under accession code SRP131209.

The following data sets were generated

Article and author information

Author details

  1. Fotini Kokou

    Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Goor Sasson

    Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Tali Nitzan

    Department of Poultry and Aquaculture, Institute of Animal Sciences, Agricultural Research Organization, Rishon LeZion, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Adi Doron-Faigenboim

    Department of Vegetable and Field Crops, Institute of Plant Science, Agricultural Research Organization, Rishon LeZion, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Sheenan Harpaz

    Department of Poultry and Aquaculture, Institute of Animal Sciences, Agricultural Research Organization, Rishon LeZion, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Avner Cnaani

    Department of Poultry and Aquaculture, Institute of Animal Sciences, Agricultural Research Organization, Rishon LeZion, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Itzhak Mizrahi

    Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    For correspondence
    imizrahi@bgu.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6636-8818

Funding

European Research Council (Grant 640384)

  • Fotini Kokou
  • Goor Sasson
  • Tali Nitzan
  • Adi Doron-Faigenboim
  • Sheenan Harpaz
  • Avner Cnaani
  • Itzhak Mizrahi

Israel Science Foundation (Grant number 1313/13)

  • Fotini Kokou
  • Goor Sasson
  • Tali Nitzan
  • Adi Doron-Faigenboim
  • Sheenan Harpaz
  • Avner Cnaani
  • Itzhak Mizrahi

Ministry of Agriculture and Rural Development (Grant number 863-0045)

  • Fotini Kokou
  • Goor Sasson
  • Tali Nitzan
  • Adi Doron-Faigenboim
  • Sheenan Harpaz
  • Avner Cnaani
  • Itzhak Mizrahi

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

Ethics

Animal experimentation: This study was approved by the Agricultural Research Organization Committee for Ethics in Using Experimental Animals and was carried out in compliance with the current laws governing biological research in Israel (Approval number: 146/09IL).

Reviewing Editor

  1. Rob Knight, University of California, San Diego, United States

Publication history

  1. Received: March 5, 2018
  2. Accepted: November 6, 2018
  3. Accepted Manuscript published: November 20, 2018 (version 1)
  4. Version of Record published: December 3, 2018 (version 2)

Copyright

© 2018, Kokou 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

  • 4,355
    Page views
  • 681
    Downloads
  • 46
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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. Fotini Kokou
  2. Goor Sasson
  3. Tali Nitzan
  4. Adi Doron-Faigenboim
  5. Sheenan Harpaz
  6. Avner Cnaani
  7. Itzhak Mizrahi
(2018)
Host genetic selection for cold tolerance shapes microbiome composition and modulates its response to temperature
eLife 7:e36398.
https://doi.org/10.7554/eLife.36398

Further reading

    1. Genetics and Genomics
    2. Microbiology and Infectious Disease
    Liselot Dewachter et al.
    Research Article

    Antibiotic resistance in the important opportunistic human pathogen Streptococcus pneumoniae is on the rise. This is particularly problematic in the case of the β-lactam antibiotic amoxicillin, which is the first-line therapy. It is therefore crucial to uncover targets that would kill or resensitize amoxicillin-resistant pneumococci. To do so, we developed a genome-wide, single-cell based, gene silencing screen using CRISPR interference called sCRilecs-seq (subsets of CRISPR interference libraries extracted by fluorescence activated cell sorting coupled to next generation sequencing). Since amoxicillin affects growth and division, sCRilecs-seq was used to identify targets that are responsible for maintaining proper cell size. Our screen revealed that downregulation of the mevalonate pathway leads to extensive cell elongation. Further investigation into this phenotype indicates that it is caused by a reduced availability of cell wall precursors at the site of cell wall synthesis due to a limitation in the production of undecaprenyl phosphate (Und-P), the lipid carrier that is responsible for transporting these precursors across the cell membrane. The data suggest that, whereas peptidoglycan synthesis continues even with reduced Und-P levels, cell constriction is specifically halted. We successfully exploited this knowledge to create a combination treatment strategy where the FDA-approved drug clomiphene, an inhibitor of Und-P synthesis, is paired up with amoxicillin. Our results show that clomiphene potentiates the antimicrobial activity of amoxicillin and that combination therapy resensitizes amoxicillin-resistant S. pneumoniae. These findings could provide a starting point to develop a solution for the increasing amount of hard-to-treat amoxicillin-resistant pneumococcal infections.

    1. Microbiology and Infectious Disease
    Dallas L Mould et al.
    Research Article Updated

    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 (LOF) 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.