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.