Cyclic di-GMP differentially tunes a bacterial flagellar motor through a novel class of CheY-like regulators

Abstract

The flagellar motor is a sophisticated rotary machine facilitating locomotion and signal transduction. Owing to its important role in bacterial behavior, its assembly and activity are tightly regulated. For example, chemotaxis relies on a sensory pathway coupling chemical information to rotational bias of the motor through phosphorylation of the motor switch protein CheY. Using a chemical proteomics approach, we identified a novel family of CheY-like (Cle) proteins in Caulobacter crescentus, which tune flagellar activity in response to binding of the second messenger c-di-GMP to a C-terminal extension. In their c-di-GMP bound conformation Cle proteins interact with the flagellar switch to control motor activity. We show that individual Cle proteins have adopted discrete cellular functions by interfering with chemotaxis and by promoting rapid surface attachment of motile cells. This study broadens the regulatory versatility of bacterial motors and unfolds mechanisms that tie motor activity to mechanical cues and bacterial surface adaptation.

Article and author information

Author details

  1. Jutta Nesper

    Focal Area of Infection Biology, Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Isabelle Hug

    Focal Area of Infection Biology, Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Setsu Kato

    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Chee-Seng Hee

    Focal Area of Structural Biology and Biophysics, Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Judith Maria Habazettl

    Focal Area of Structural Biology and Biophysics, Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Pablo Manfredi

    Focal Area of Infection Biology, Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Stephan Grzesiek

    Focal Area of Structural Biology and Biophysics, Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  8. Tilman Schirmer

    Focal Area of Structural Biology and Biophysics, Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  9. Thierry Emonet

    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6746-6564
  10. Urs Jenal

    Focal Area of Infection Biology, Biozentrum, University of Basel, Basel, Switzerland
    For correspondence
    urs.jenal@unibas.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1637-3376

Funding

European Research Council (Advanced Research Grant to U.J.)

  • Urs Jenal

Paul G. Allen Family Foundation (award no. 11562)

  • Thierry Emonet

Swiss National Science Foundation (Sinergia grant CRSII3_127433)

  • Urs Jenal

National Institutes of Health (grant no. 1R01GM106189)

  • Thierry Emonet

Swiss National Science Foundation (grant 31003A_166652)

  • Tilman Schirmer

Swiss National Science Foundation (grant 31003A_173089)

  • Stephan Grzesiek

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

Copyright

© 2017, Nesper 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

  • 3,618
    views
  • 674
    downloads
  • 65
    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. Jutta Nesper
  2. Isabelle Hug
  3. Setsu Kato
  4. Chee-Seng Hee
  5. Judith Maria Habazettl
  6. Pablo Manfredi
  7. Stephan Grzesiek
  8. Tilman Schirmer
  9. Thierry Emonet
  10. Urs Jenal
(2017)
Cyclic di-GMP differentially tunes a bacterial flagellar motor through a novel class of CheY-like regulators
eLife 6:e28842.
https://doi.org/10.7554/eLife.28842

Share this article

https://doi.org/10.7554/eLife.28842

Further reading

    1. Genetics and Genomics
    2. Microbiology and Infectious Disease
    Louna Fruchard, Anamaria Babosan ... Zeynep Baharoglu
    Research Article

    Tgt is the enzyme modifying the guanine (G) in tRNAs with GUN anticodon to queuosine (Q). tgt is required for optimal growth of Vibrio cholerae in the presence of sub-lethal aminoglycoside concentrations. We further explored here the role of the Q34 in the efficiency of codon decoding upon tobramycin exposure. We characterized its impact on the overall bacterial proteome, and elucidated the molecular mechanisms underlying the effects of Q34 modification in antibiotic translational stress response. Using molecular reporters, we showed that Q34 impacts the efficiency of decoding at tyrosine TAT and TAC codons. Proteomics analyses revealed that the anti-SoxR factor RsxA is better translated in the absence of tgt. RsxA displays a codon bias toward tyrosine TAT and overabundance of RsxA leads to decreased expression of genes belonging to SoxR oxidative stress regulon. We also identified conditions that regulate tgt expression. We propose that regulation of Q34 modification in response to environmental cues leads to translational reprogramming of transcripts bearing a biased tyrosine codon usage. In silico analysis further identified candidate genes which could be subject to such translational regulation, among which DNA repair factors. Such transcripts, fitting the definition of modification tunable transcripts, are central in the bacterial response to antibiotics.

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

    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.