Metabolite transporters in trypanosomatid parasites: promising therapeutic targets but... How to deal with them?

Abstract

Infections caused by protozoan parasites are one of the most important public health problems in developing countries. One approach to design new drugs for these parasitic diseases relies on metabolic and molecular features which are ideally absent in mammalian hosts. Out of them, nutrient transporters play an important role since they were subjected to millions of years of adaptation to parasitism, in which this protozoan replaced many biosynthetic routes for transport systems. Here we address the current knowledge of trypanosomatids transport systems and the molecules related to such processes, including a description of permeases involved in drug uptake, and also those responsible of drug resistance. The latter process produces, in many cases, the treatment failure due to the loss of the transporter function, as is the case of eflornithine, as well as by increasing the extrusion of drugs, in which usually ABC-type transporters are involved. All these aspects and the perspectives on this topic are briefly updated in this review.