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 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.
Bray
Patrick G
PG
Molecular and Biochemical Parasitology Group, Liverpool School of Tropical Medicine, Liverpool, L3 5QS, UK.
Barrett
Michael P
MP
Ward
Stephen A
SA
de Koning
Harry P
HP
D000818:Animals; D000981:Antiprotozoal Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D006801:Humans; D007894:Leishmania mexicana / Q000187:drug effects* / Q000378:metabolism; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000517:prevention & control; D010419:Pentamidine / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000517:prevention & control
D000981:Antiprotozoal Agents; D010419:Pentamidine