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Updated: Apr 17, 2026

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
Published on: August 17, 2019
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.
Abstract:
ATP up-regulates macrophage antimycobacterial activity in a P2X7-dependent manner, but little is known about whether ATP directly exhibits antimicrobial effects against intracellular mycobacteria. In this study, we found that ATP inhibited the growth of various bacteria, including Staphylococcus, Pseudomonas, and mycobacteria, without damaging bacterial surface structures. Using gene technology, we newly established an enterobactin-deficient (entB(-)) mutant from ATP-resistant Klebsiella pneumoniae, and found the recovery of ATP susceptibility in the enterobactin-deleted mutant. Therefore, ATP's antibacterial activity is attributable to its iron-chelating ability. Since ATP distributed in the cytosol of macrophages at high concentrations, ATP appears to augment macrophage's antimicrobial activity by directly attacking intracytosolic and intra-autophagosomal pathogens. Furthermore, ATP exhibited combined effects with some antimicrobials against methicillin-resistant S. aureus (MRSA) and M. intracellulare, suggesting its usefulness as an adjunctive drug in the chemotherapy of certain intractable infections.
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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