1. Genetics and Genomics
  2. Microbiology and Infectious Disease
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An analog to digital converter controls bistable transfer competence of a widespread integrative and conjugative element

  1. Nicolas Carraro
  2. Xavier Richard
  3. Sandra Sulser
  4. Francois Delavat
  5. Christian Mazza
  6. Jan Roelof van der Meer  Is a corresponding author
  1. University of Lausanne, Switzerland
  2. University of Fribourg, Switzerland
Research Article
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Cite this article as: eLife 2020;9:e57915 doi: 10.7554/eLife.57915

Abstract

Conjugative transfer of the integrative and conjugative element ICEclc in Pseudomonas requires development of a transfer competence state in stationary phase, which arises only in 3-5% of individual cells. The mechanisms controlling this bistable switch between non-active and transfer competent cells have long remained enigmatic. Using a variety of genetic tools and epistasis experiments in P. putida, we uncovered an 'upstream' cascade of three consecutive transcription factor-nodes, which controls transfer competence initiation. One of the uncovered transcription factors (named BisR) is representative for a new regulator family. Initiation activates a feedback loop, controlled by a second hitherto unrecognized heteromeric transcription factor named BisDC. Stochastic modeling and experimental data demonstrated the feedback loop to act as a scalable converter of unimodal (population-wide or 'analog') input to bistable (subpopulation-specific or ‘digital’) output. The feedback loop further enables prolonged production of BisDC, which ensures expression of the 'downstream' functions mediating ICE transfer competence in activated cells. Phylogenetic analyses showed that the ICEclc regulatory constellation with BisR and BisDC is widespread among Gamma- and Beta-proteobacteria, including various pathogenic strains, highlighting its evolutionary conservation and prime importance to control the behaviour of this wide family of conjugative elements.

Article and author information

Author details

  1. Nicolas Carraro

    Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6364-547X
  2. Xavier Richard

    Department of Mathematics, University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Sandra Sulser

    Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Francois Delavat

    Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5985-4583
  5. Christian Mazza

    Department of Mathematics, University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Jan Roelof van der Meer

    Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
    For correspondence
    JanRoelof.VanDerMeer@unil.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1485-3082

Funding

Swiss National Science Foundation (31003A_175638)

  • Jan Roelof van der Meer

SystemsX.ch (Interdisciplinary Grant)

  • Christian Mazza

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

Reviewing Editor

  1. Eva Top

Publication history

  1. Received: April 15, 2020
  2. Accepted: July 24, 2020
  3. Accepted Manuscript published: July 28, 2020 (version 1)
  4. Version of Record published: August 12, 2020 (version 2)

Copyright

© 2020, Carraro 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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