title: ATP exhibits antimicrobial action by inhibiting bacterial utilization of ferric ions.
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.
authors.affiliation: Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo 693-8501, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tatano
authors.affiliation: Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo 693-8501, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kanehiro
authors.affiliation: Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo 693-8501, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Sano
authors.affiliation: Department of Nutrition Administration, Yasuda Women's University, Hiroshima 231-0153, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: 1] Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo 693-8501, Japan [2] Faculty of Nursing, Yasuda Women's University, Hiroshima 231-0153, Japan.
authors.forename: Haruaki
authors.initials: H
authors.lastname: Tomioka
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D004336:Drug Antagonism; D004357:Drug Synergism; D007477:Ions / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D017262:Siderophores / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D007477:Ions; D007502:Iron Chelating Agents; D017262:Siderophores; D000255:Adenosine Triphosphate; D007501:Iron