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Studying Copper Nanoparticle-Induced Programmed Cell Death in Bacteria
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Copper ions inhibit pentose phosphate pathway function in Staphylococcus aureus.

Javiera Norambuena1, Hassan Al-Tameemi1, Hannah Bovermann1

  • 1Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey, United States of America.

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Copper (Cu) ions inhibit Staphylococcus aureus growth by disrupting phosphoribosyl diphosphate (PRPP) synthesis, a key metabolic pathway. This disruption impairs bacterial colonization, suggesting a role for copper in host defense against infection.

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Area of Science:

  • Microbiology
  • Cell Biology
  • Biochemistry

Background:

  • Copper (Cu) is essential but toxic at high concentrations.
  • Staphylococcus aureus possesses systems to detoxify Cu ions.
  • The precise mechanisms of Cu toxicity in S. aureus are not fully understood.

Purpose of the Study:

  • To elucidate the cellular mechanisms by which Cu ions exert toxicity in S. aureus.
  • To investigate the role of phosphoribosyl diphosphate (PRPP) metabolism in Cu resistance.
  • To assess the impact of Cu detoxification deficiency on S. aureus virulence.

Main Methods:

  • Metabolomic analysis of Cu-exposed S. aureus strains lacking detoxification systems.
  • Genetic screening to identify mutations conferring Cu resistance.
  • Enzyme activity assays and gene expression analysis.
  • Murine models of acute pneumonia and skin infection.

Main Results:

  • Cu(II) exposure increased metabolites for PRPP synthesis in Cu-detoxification deficient strains.
  • A mutation in adenine phosphoribosyltransferase (apt) conferred Cu resistance by altering PRPP utilization.
  • Phosphoribosylpyrophosphate synthetase (Prs) was inhibited by Cu ions in vitro and in vivo, reducing PRPP levels.
  • S. aureus strains lacking Cu detoxification were impaired in airway and skin colonization.

Conclusions:

  • Cu ions inhibit S. aureus growth by targeting the pentose phosphate pathway via Prs inhibition.
  • Altered PRPP metabolism influences Cu sensitivity in S. aureus.
  • Defective Cu detoxification compromises S. aureus virulence in host infections.
  • Cu ions may be utilized by the immune system to control S. aureus infections.