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Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus

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 a...

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Autores principales: Corrigan, Rebecca M., Bowman, Lisa, Willis, Alexandra R., Kaever, Volkhard, Gründling, Angelika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342491/
https://www.ncbi.nlm.nih.gov/pubmed/25575594
http://dx.doi.org/10.1074/jbc.M114.598300
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author Corrigan, Rebecca M.
Bowman, Lisa
Willis, Alexandra R.
Kaever, Volkhard
Gründling, Angelika
author_facet Corrigan, Rebecca M.
Bowman, Lisa
Willis, Alexandra R.
Kaever, Volkhard
Gründling, Angelika
author_sort Corrigan, Rebecca M.
collection PubMed
description 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.
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spelling pubmed-43424912015-03-02 Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus Corrigan, Rebecca M. Bowman, Lisa Willis, Alexandra R. Kaever, Volkhard Gründling, Angelika J Biol Chem Microbiology 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. American Society for Biochemistry and Molecular Biology 2015-02-27 2015-01-09 /pmc/articles/PMC4342491/ /pubmed/25575594 http://dx.doi.org/10.1074/jbc.M114.598300 Text en © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles
spellingShingle Microbiology
Corrigan, Rebecca M.
Bowman, Lisa
Willis, Alexandra R.
Kaever, Volkhard
Gründling, Angelika
Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus
title Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus
title_full Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus
title_fullStr Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus
title_full_unstemmed Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus
title_short Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus
title_sort cross-talk between two nucleotide-signaling pathways in staphylococcus aureus
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342491/
https://www.ncbi.nlm.nih.gov/pubmed/25575594
http://dx.doi.org/10.1074/jbc.M114.598300
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