ArticleThe Journal of biological chemistry2015
Cross-talk between two nucleotide-signaling pathways in Staphylococcus aureus.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 144 citations in OpenAlex.
- Mislocalization of PBPs inMicrobiology spectrum · 2026Article
- Cyclic di-AMP signaling and regulation inmSphere · 2026Review
- A global stress alarmone couples nutrient limitation to suppression of social signaling in bacteria.iScience · 2026Article
- Statin-induced lipid carrier stress reveals a conserved vulnerability in β-lactam-resistant Gram-positive bacteria.Nature communications · 2026Article
- BeyondAntimicrobial agents and chemotherapy · 2026Article
- Article
- Determining the Importance of the Stringent Response for Methicillin-Resistant Staphylococcus aureus Virulence In Vivo.The Journal of infectious diseases · 2025Article
- Cyclic-di-AMP modulates cellular turgor in response to defects in bacterial cell wall synthesis.Nature microbiology · 2025Article
- Impact of c-di-AMP Accumulation, L-cysteine, and Oxygen on Catalase Activity and Oxidative Stress Resistance ofMicroorganisms · 2025Article
- Skin mycobiota-mediated antagonism against Staphylococcus aureus through a modified fatty acid.Current biology : CB · 2025Article
- (p)ppGpp-mediated GTP homeostasis ensures survival and antibiotic tolerance of Staphylococcus aureus.Communications biology · 2025Article
- Biofilm formation byProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Two codependent routes lead to high-level MRSA.Science (New York, N.Y.) · 2024Article
- Article
- Bacterial cell volume regulation and the importance of cyclic di-AMP.Microbiology and molecular biology reviews : MMBR · 2024Review
- Review
- mSphere of Influence: Targeting bacterial signaling and metabolism to overcome antimicrobial resistance.mSphere · 2024Article
- Coordinated regulation of osmotic imbalance by c-di-AMP shapes ß-lactam tolerance in Group BmicroLife · 2024Article
- Histidine transport is essential for the growth of Staphylococcus aureus at low pH.PLoS pathogens · 2024Article
- Crosstalk between (p)ppGpp and other nucleotide second messengers.Current opinion in microbiology · 2023Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.