Functional analysis of Leishmania membrane (Non-ABC) transporters involved in drug resistance

Leishmania parasites rely heavily upon membrane transport proteins to deliver essential nutrients from their hosts to the interior of the parasite. Some of these transporters also serve as routes for uptake of drugs used for treatment of leishmaniasis or experimental drugs with potential for development of novel anti-leishmanial therapies. Hence, mutations within the coding regions of such permeases or alterations in the expression of the carrier proteins can confer drug resistance upon the parasites. This chapter reviews the current level of knowledge regarding several classes of membrane transporters known to play roles in uptake or sensitivity to drugs. The increasing knowledge of the "permeome," provided by complete genome sequences of several Leishmania species, has advanced considerably our knowledge of how nutrients and drugs or other cytotoxic compounds enter these pathogenic protozoa. Recent genome-wide approaches to functional analysis promise to further our understanding of transporters as determinants of drug sensitivity and resistance.