Evaluation of Purine Salvage as a Chemotherapeutic Target in the Plasmodium Yoelli Rodent Model
Abstract
Because resistance to current antimalarials is widespread, new targets for malaria chemotherapy are needed to protect military personnel stationed in developing countries. Malaria parasites cannot make purines needed for RNA and DNA and must salvage purines from their host. Our preliminary studies reveal purine salvage is unique in malaria parasites. We would like to determine whether the unique activities of the malaria enzymes can be exploited to develop specific treatments for malaria that will be effective but not toxic. While study of drug targets in vivo is critical for all infectious diseases, evaluation in an animal model is especially critical for evaluation of purine salvage as a drug target. We perform our studies in Plasmodium yoelii, a rodent malaria whose genome has been sequenced and for which there are techniques for genetic manipulation. We have refined techniques for transformation of this rodent malaria species and have developed GFP reporter parasite lines. Using this system we have genetically disrupted purine salvage enzyme purine nucleoside phosphorylase (PNP) and are attempting to disrupt adenosine deaminase (ADA). We are testing the effects of malaria-specific PNP inhibitors on malaria infection in mice. These novel drugs will be tested in combination with other antimalarials and will also be evaluated for efficacy against exoerythrocytic malaria forms. We hope these experiments will lead to the development of new effective and nontoxic agents that can protect our military personnel from the lethal effects of malaria infection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2006
- Accession Number
- ADA452219
Entities
People
- Kami Kim
Organizations
- Albert Einstein College of Medicine