ATP exhibits antimicrobial action by inhibiting bacterial utilization of ferric ions

Yutaka Tatano1, Yuichi Kanehiro1, Chiaki Sano1

  • 1Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo 693-8501, Japan.

Scientific Reports
|February 26, 2015
PubMed

Insights

Adenosine triphosphate (ATP) directly inhibits bacterial growth by chelating iron, enhancing macrophage antimicrobial activity against intracellular pathogens. This suggests ATP

Area of Science:

  • Microbiology
  • Immunology
  • Biochemistry

Background:

  • Adenosine triphosphate (ATP) is known to enhance macrophage antimycobacterial activity via P2X7 receptors.
  • The direct antimicrobial effects of ATP against intracellular bacteria remain largely uncharacterized.

Purpose of the Study:

  • To investigate the direct antimicrobial activity of ATP against various bacteria, including mycobacteria.
  • To elucidate the mechanism underlying ATP's antibacterial action.
  • To explore ATP's potential as an adjunctive therapeutic agent.

Main Methods:

  • ATP susceptibility testing on wild-type and enterobactin-deficient (entB(-)) Klebsiella pneumoniae mutants.
  • Assessment of ATP's effect on bacterial surface structures.
  • Evaluation of ATP's combined effects with antimicrobials against resistant strains.

Main Results:

  • ATP inhibited the growth of Staphylococcus, Pseudomonas, and mycobacteria without damaging bacterial surfaces.
  • An enterobactin-deficient mutant of Klebsiella pneumoniae regained susceptibility to ATP, indicating iron chelation as the mechanism.
  • ATP demonstrated synergistic effects with certain antimicrobials against MRSA and M. intracellulare.

Conclusions:

  • ATP possesses direct antibacterial activity mediated by its iron-chelating properties.
  • Intracellular ATP may contribute to macrophage defense against pathogens within the cytosol and autophagosomes.
  • ATP shows promise as an adjunctive therapy for intractable infections, including those caused by MRSA.

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