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Action of deferoxamine against Pneumocystis carinii

A B Clarkson1, D Turkel-Parrella, J H Williams

  • 1Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10016, USA. clarka01@nyu.edu

Antimicrobial Agents and Chemotherapy
|November 16, 2001
PubMed

Insights

Deferoxamine (DFO) directly damages Pneumocystis pneumonia (PCP) pathogens, not just by iron deprivation. Weekly aerosolized DFO proved 100% effective for preventing and treating PCP in a rat model.

Area of Science:

  • Medical Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Deferoxamine (DFO), an iron overload drug, previously showed activity against Pneumocystis carinii pneumonia (PCP) in rats.
  • The presumed mechanism of action was iron deprivation, but this study investigated a direct cellular effect.

Purpose of the Study:

  • To elucidate the mode of action of deferoxamine (DFO) against Pneumocystis carinii.
  • To evaluate the efficacy of aerosolized DFO for Pneumocystis pneumonia (PCP) treatment and prophylaxis.

Main Methods:

  • Deferoxamine (DFO) uptake by P. carinii was measured using high-pressure liquid chromatography.
  • Intracellular free iron levels were assessed using calcein-AM.
  • In vitro growth inhibition and cell death assays were performed.
  • Efficacy of weekly aerosolized DFO was tested in a rat model of PCP for prophylaxis and treatment.

Main Results:

  • Deferoxamine (DFO) penetrates P. carinii and reduces intracellular free iron.
  • Exposure to DFO leads to irreversible damage, cessation of growth, and cell number decline.
  • Weekly aerosol administration of DFO was 100% effective in preventing and curing PCP in rats.

Conclusions:

  • Deferoxamine (DFO) exerts a direct, irreversible cytotoxic effect on P. carinii.
  • Infrequent aerosolized DFO delivery is a highly effective strategy for PCP treatment and prophylaxis in an animal model.

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