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Antimicrobial Agents and Chemotherapy, December 2001, p. 3560-3565, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3560-3565.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Action of Deferoxamine against Pneumocystis carinii

Allen B. Clarkson Jr.,1,* David Turkel-Parrella,1 Jonathan H. Williams,1 Lung Chi Chen,2 Terry Gordon,2 and Salim Merali1

Department of Medical and Molecular Parasitology1 and Department of Environmental Medicine,2 New York University School of Medicine, New York, New York 10016

Received 27 June 2001/Returned for modification 21 August 2001/Accepted 20 September 2001

We found earlier that deferoxamine (DFO), a drug used for treatment of iron overload, is active against a rat model of Pneumocystis carinii pneumonia (PCP). We had assumed a mode of action by deprivation of nutritional iron; however, data here show that DFO penetrates P. carinii, causing irreversible damage, thus indicating a different mode of action. Penetration was demonstrated by showing DFO uptake by high-pressure liquid chromatography analysis. By using calcein-AM as an indicator, exposure to DFO was shown to cause a reduction in P. carinii cytoplasmic free iron. Exposure to >= 100 µM DFO for >= 8 h in vitro caused growth to cease and cell numbers to decline over several days. This direct and irreversible damage to P. carinii led to the prediction that infrequent delivery of DFO to the lungs via an aerosol would be an effective treatment in the animal model of PCP. This prediction was confirmed by demonstrating that a once-a-week aerosol treatment of rats was 100% effective both as a prophylactic and as a curative treatment in a rat model of PCP.

* Corresponding author. Mailing address: Department of Medical and Molecular Parasitology, New York University School of Medicine, 341 East 25th St., New York, NY 10010. Phone: (212) 263-6637. Fax: (212) 263-6637 (autoswitch). E-mail: clarka01{at}nyu.edu.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3560-3565, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3560-3565.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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