PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoM
- Robert Koch Institute, Germany
- Newcastle University, United Kingdom
- University of Göttingen, Germany
- 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.
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PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoMEuropean Nucleotide Archive, PRJEB35110.
Article and author information
Author details
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
© 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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PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoM
eLife 9:e56048.
https://doi.org/10.7554/eLife.56048
