Pentamidine uptake and resistance in pathogenic protozoa: past, present and future

Diamidines, and pentamidine in particular, have a long history as valuable chemotherapeutic agents against infectious disease. Their selectivity is due mostly to selective accumulation by the pathogen, rather than the host cell; and acquired resistance is frequently the result of changes in transmem...

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Bibliographic Details
Published in:Trends in parasitology 2003-05, Vol.19 (5), p.232-239
Main Authors: Bray, Patrick G., Barrett, Michael P., Ward, Stephen A., de Koning, Harry P.
Format: Article
Language:English
Subjects:
Animals
Antiprotozoal Agents - metabolism
Antiprotozoal Agents - pharmacology
Antiprotozoal Agents - therapeutic use
Biochemistry. Physiology. Immunology. Molecular biology
Biological and medical sciences
Drug Resistance
Fundamental and applied biological sciences. Psychology
Humans
Leishmania mexicana - drug effects
Leishmania mexicana - metabolism
Leishmaniasis, Cutaneous - drug therapy
Malaria, Falciparum - drug therapy
Malaria, Falciparum - prevention & control
Pentamidine - metabolism
Pentamidine - pharmacology
Pentamidine - therapeutic use
Plasmodium falciparum - drug effects
Plasmodium falciparum - metabolism
Protozoa
Trypanosoma brucei brucei - drug effects
Trypanosoma brucei brucei - metabolism
Trypanosomiasis, African - drug therapy
Trypanosomiasis, African - prevention & control
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Summary:Diamidines, and pentamidine in particular, have a long history as valuable chemotherapeutic agents against infectious disease. Their selectivity is due mostly to selective accumulation by the pathogen, rather than the host cell; and acquired resistance is frequently the result of changes in transmembrane transport of the drug. Here, recent progress in elucidating the mechanisms of diamidine transport in three important protozoan pathogens, Trypanosoma brucei, Leishmania and Plasmodium falciparum, is reviewed, and the implications for drug resistance are discussed.
ISSN:1471-4922
1471-5007
DOI:10.1016/S1471-4922(03)00069-2