1704 Purine Salvage in Giard 1 a Lamblia

Abstract

Giardia lamblia is an anaerobic flagellated protozoa and a common inhabitant of human intestine. It is transmitted mainly by ingestion of the cysts in contaminated food or drinking water, and is present in at least 10% of the population in the United States (1). The infection causes diarrhea, abdominal pain, weight loss, and retarded growth in children. Tbe infectious dose of cysts appears to be quite low, whereas a large number of cysts can be shed from infected individuals. Metronidazole (Flagyl) and atabrine are the only two drugs available for treating the infection; both having undesirable side effects (2). No chemoprophylactic drugs are yet available for giardiasis. Recent success in establishing axenic cultures of G. lamblia trophozoites (3) has made it possible to study the metabolisms in this organism. In one recent report (4), G. lamblia was found incapable of incorporating orotic and aspartic acid into nucleic acids, and no activities of de novo pyrimidine-synthesis enzymes were detected in the crude extracts of G. lamblia. This finding, which suggests the absence of pyrimidine de novo synthesis in G. lamblia, agrees with our recent observations on two other anaerobic, flagellated protozoan parasites, Tritrichomonasfoetus (5) and Trichomonas vaginalis (6). These two parasites are unable to synthesize pyrimidines de novo but rely on salvaging uracil (5) or cytidine and uridine (6) for their requirement for pyrimidine ribonucleotides. They have no detectable dihydrofolate reductase or thymidylate synthetase activity; TMP can be only acquired via the action of a unique enzyme, thymidine phosphotransferase, for salvaging exogenous thymidine. Preliminary studies in this laboratory also indicated the absence of dihydrofolate reductase and thymidylate synthetase in G. lamblia (Wang, unpublished results). Tbymidine salvage by these three parasites thus could be an attractive target for chemotherapeutic control of these three parasites. On the other hand, T. foetus (7) and T. vaginalis (8) have also been found incapable of de novo synthesis ofpurine nucleotides, as would have been expected from the absence of dihydrofolate reductase. It is thus likely that G. lamblia may lack this synthetic capability. In fact, all the protozoan parasites investigated to date appear to lack the activity in de novo purine synthesis and depend solely on purine salvage for purine nucleotides (7-9). This common deficiency among parasites has provided ample opportunities for chemotherapeutic attack. Allopurinol is effective against Trypanosoma cruzi because the drug is recognized as a

4 Figures and Tables

Cite this paper

@inproceedings{Wang20031704PS, title={1704 Purine Salvage in Giard 1 a Lamblia}, author={Ching C. Wang and S M Aldritt}, year={2003} }