PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoM

Abstract
Data availability
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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

1. Wamp S
2. Rutter ZJ
3. Rismondo J
4. Jennings CE
5. Möller L
6. Lewis RJ
7. Halbedel S
(2020) PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoM
European Nucleotide Archive, PRJEB35110.

https://www.ebi.ac.uk/ena/data/search?query=PRJEB35110
1. Wamp S
2. Rutter ZJ
3. Rismondo J
4. Jennings CE
5. Möller L
6. Lewis RJ
7. Halbedel S
(2020) PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoM
Protein Data Bank, 6TIF.

https://www.ebi.ac.uk/pdbe/entry/pdb/6tif

Article and author information

Author details

Sabrina Wamp

FG11 - Division of Enteropathogenic bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany

Competing interests
The authors declare that no competing interests exist.
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.
Jeanine Rismondo

Department of General Microbiology, University of Göttingen, Göttingen, Germany

Competing interests
The authors declare that no competing interests exist.
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.
Lars Möller

ZBS 4 - Advanced Light and Electron Microscopy, Robert Koch Institute, Berlin, Germany

Competing interests
The authors declare that no competing interests exist.
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.
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.

"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.

Copyright

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.