Corrigan, R.M. orcid.org/0000-0002-6031-1148, Bowman, L., Willis, A.R. et al. (2 more authors) (2015) Cross-talk between two nucleotide-signaling pathways in Staphylococcus aureus. Journal of Biological Chemistry , 290 (9). pp. 5826-5839. ISSN 0021-9258
Abstract
Nucleotide-signaling pathways are found in all kingdoms of life and are utilized to coordinate a rapid response to external stimuli. The stringent response alarmones guanosine tetra- (ppGpp) and pentaphosphate (pppGpp) control a global response allowing cells to adapt to starvation conditions such as amino acid depletion. One more recently discovered signaling nucleotide is the secondary messenger cyclic diadenosine monophosphate (c-di-AMP). Here, we demonstrate that this signaling nucleotide is essential for the growth of Staphylococcus aureus, and its increased production during late growth phases indicates that c-di-AMP controls processes that are important for the survival of cells in stationary phase. By examining the transcriptional profile of cells with high levels of c-di-AMP, we reveal a significant overlap with a stringent response transcription signature. Examination of the intracellular nucleotide levels under stress conditions provides further evidence that high levels of c-di-AMP lead to an activation of the stringent response through a RelA/SpoT homologue (RSH) enzyme-dependent increase in the (p)ppGpp levels. This activation is shown to be indirect as c-di-AMP does not interact directly with the RSH protein. Our data extend this interconnection further by showing that the S. aureus c-di-AMP phosphodiesterase enzyme GdpP is inhibited in a dose-dependent manner by ppGpp, which itself is not a substrate for this enzyme. Altogether, these findings add a new layer of complexity to our understanding of nucleotide signaling in bacteria as they highlight intricate interconnections between different nucleotide-signaling networks.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Available under Creative Commons Attribution Unported License (https://creativecommons.org/licenses/by/3.0/). |
Keywords: | Bacterial Signal Transduction; Cyclic Nucleotide; Gene Regulation; Microarray; Phosphodiesterases; staphylococcus aureus (S. aureus); Stress Response |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 22 Mar 2017 16:33 |
Last Modified: | 22 Mar 2017 16:33 |
Published Version: | https://doi.org/10.1074/jbc.M114.598300 |
Status: | Published |
Publisher: | American Society for Biochemistry and Molecular Biology |
Refereed: | Yes |
Identification Number: | 10.1074/jbc.M114.598300 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110398 |
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