PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoM

  1. Sabrina Wamp
  2. Zoe J Rutter
  3. Jeanine Rismondo
  4. Claire E Jennings
  5. Lars Möller
  6. Richard J Lewis
  7. Sven Halbedel  Is a corresponding author
  1. Robert Koch Institute, Germany
  2. Newcastle University, United Kingdom
  3. University of Göttingen, Germany
  4. Northern Institute for Cancer Research, United Kingdom

Abstract

Peptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that sense PG fragments. However, only a few PG biosynthetic enzymes are direct kinase substrates. Here, we identify the conserved ReoM protein as a novel PASTA-eSTK substrate in the Gram-positive pathogen Listeria monocytogenes. Our data show that the phosphorylation of ReoM is essential as it controls ClpCP-dependent proteolytic degradation of the essential enzyme MurA, which catalyses the first committed step in PG biosynthesis. We also identify ReoY as a second novel factor required for degradation of ClpCP substrates. Collectively, our data imply that the first committed step of PG biosynthesis is activated through control of ClpCP protease activity in response to signals of PG homeostasis imbalance.

Data availability

Genome sequences of shg8, shg10, shg12 and LMSW76 were deposited at ENA under study number PRJEB35110 and sample accession numbers ERS3927571 (SAMEA6127277), ERS3927572 (SAMEA6127278), ERS3927573 (SAMEA6127279), and ERS3967687 (SAMEA6167687) respectively.The co-ordinates and structure factors for the crystal structure of ReoM have been deposited at PDBe with accession code 6TIF.

The following data sets were generated

Article and author information

Author details

  1. Sabrina Wamp

    FG11 - Division of Enteropathogenic bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Zoe J Rutter

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Jeanine Rismondo

    Department of General Microbiology, University of Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Claire E Jennings

    Newcastle Drug Discovery, Northern Institute for Cancer Research, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Lars Möller

    ZBS 4 - Advanced Light and Electron Microscopy, Robert Koch Institute, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Richard J Lewis

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Sven Halbedel

    FG11 - Division of Enteropathogenic bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany
    For correspondence
    halbedels@rki.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5575-8973

Funding

Deutsche Forschungsgemeinschaft (HA 6830/1-1)

  • Sven Halbedel

Deutsche Forschungsgemeinschaft (HA 6830/1-2)

  • Sven Halbedel

Fonds der chemischen Industrie (661460)

  • Sven Halbedel

Biotechnology and Biological Sciences Research Council (BB/M011186/1)

  • Richard J Lewis

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

Reviewing Editor

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Publication history

  1. Received: February 14, 2020
  2. Accepted: May 27, 2020
  3. Accepted Manuscript published: May 29, 2020 (version 1)
  4. Version of Record published: June 10, 2020 (version 2)

Copyright

© 2020, Wamp 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. Sabrina Wamp
  2. Zoe J Rutter
  3. Jeanine Rismondo
  4. Claire E Jennings
  5. Lars Möller
  6. Richard J Lewis
  7. Sven Halbedel
(2020)
PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoM
eLife 9:e56048.
https://doi.org/10.7554/eLife.56048

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