Homeostatic control of cell wall hydrolysis by the WalRK two-component signaling pathway in Bacillus subtilis

  1. Genevieve S Dobihal
  2. Yannick R Brunet
  3. Josué Flores-Kim
  4. David Z Rudner  Is a corresponding author
  1. Harvard Medical School, United States

Abstract

Bacterial cells are encased in a peptidoglycan (PG) exoskeleton that protects them from osmotic lysis and specifies their distinct shapes. Cell wall hydrolases are required to enlarge this covalently closed macromolecule during growth, but how these autolytic enzymes are regulated remains poorly understood. Bacillus subtilis encodes two functionally redundant D,L-endopeptidases (CwlO and LytE) that cleave peptide crosslinks to allow expansion of the PG meshwork during growth. Here, we provide evidence that the essential and broadly conserved WalR-WalK two component regulatory system continuously monitors changes in the activity of these hydrolases by sensing the cleavage products generated by these enzymes and modulating their levels and activity in response. The WalR-WalK pathway is conserved among many Gram-positive pathogens where it controls transcription of distinct sets of PG hydrolases. Cell wall remodeling in these bacteria may be subject to homeostatic control mechanisms similar to the one reported here.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Genevieve S Dobihal

    Department of Microbiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7589-1133
  2. Yannick R Brunet

    Department of Microbiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Josué Flores-Kim

    Department of Microbiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8282-6647
  4. David Z Rudner

    Department of Microbiology, Harvard Medical School, Boston, United States
    For correspondence
    rudner@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0236-7143

Funding

National Institute of General Medical Sciences (GM086466)

  • David Z Rudner

National Institute of General Medical Sciences (GM127399)

  • David Z Rudner

National Institute of Allergy and Infectious Diseases (U19 AI109764)

  • David Z Rudner

National Institute of Allergy and Infectious Diseases (F32AI36431)

  • Josué Flores-Kim

European Molecular Biology Organization (Long-Term Fellowship)

  • Yannick R Brunet

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

Reviewing Editor

  1. Tâm Mignot, CNRS-Aix Marseille University, France

Publication history

  1. Received: September 21, 2019
  2. Accepted: December 5, 2019
  3. Accepted Manuscript published: December 6, 2019 (version 1)
  4. Version of Record published: January 24, 2020 (version 2)

Copyright

© 2019, Dobihal 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. Genevieve S Dobihal
  2. Yannick R Brunet
  3. Josué Flores-Kim
  4. David Z Rudner
(2019)
Homeostatic control of cell wall hydrolysis by the WalRK two-component signaling pathway in Bacillus subtilis
eLife 8:e52088.
https://doi.org/10.7554/eLife.52088

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