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Cross-talk between two nucleotide-signaling pathways in Staphylococcus aureus.

Rebecca M Corrigan1, Lisa Bowman1, Alexandra R Willis1

  • 1From the Section of Microbiology and Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, United Kingdom and.

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Summary
This summary is machine-generated.

Cyclic diadenosine monophosphate (c-di-AMP) is essential for Staphylococcus aureus growth and survival. High c-di-AMP levels activate the stringent response indirectly, revealing complex bacterial nucleotide signaling networks.

Keywords:
Bacterial Signal TransductionCyclic NucleotideGene RegulationMicroarrayPhosphodiesterasesStress Responsestaphylococcus aureus (S. aureus)

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Area of Science:

  • Bacterial Physiology
  • Molecular Biology
  • Microbial Pathogenesis

Background:

  • Nucleotide signaling pathways coordinate cellular responses to environmental stimuli.
  • The stringent response, mediated by guanosine tetra- (ppGpp) and pentaphosphate (pppGpp), enables bacterial adaptation to starvation.
  • Cyclic diadenosine monophosphate (c-di-AMP) is a recently identified secondary messenger with crucial roles in bacterial physiology.

Purpose of the Study:

  • To investigate the role of c-di-AMP in Staphylococcus aureus growth and survival.
  • To elucidate the relationship between c-di-AMP and the stringent response in S. aureus.
  • To understand the regulatory mechanisms connecting different bacterial nucleotide signaling networks.

Main Methods:

  • Analysis of transcriptional profiles in response to varying c-di-AMP levels.
  • Measurement of intracellular nucleotide concentrations under stress conditions.
  • Enzymatic assays to determine the interaction between c-di-AMP, ppGpp, and the GdpP enzyme.

Main Results:

  • c-di-AMP is essential for S. aureus growth and its elevated production supports stationary phase survival.
  • High c-di-AMP levels induce a transcriptional signature overlapping with the stringent response.
  • c-di-AMP indirectly activates the stringent response via RelA/SpoT homologue (RSH) enzymes and increased (p)ppGpp levels.
  • The S. aureus c-di-AMP phosphodiesterase GdpP is inhibited by ppGpp.

Conclusions:

  • c-di-AMP plays a critical role in S. aureus growth and stress adaptation.
  • A novel regulatory link exists between c-di-AMP and the stringent response, mediated by RSH enzymes.
  • ppGpp directly inhibits the c-di-AMP degrading enzyme GdpP, highlighting intricate nucleotide signaling crosstalk in bacteria.