Genetic dissection of drug resistance in trypanosomes | Full Text
Part of a special edition of Parasitology, 140(12): Genetic and genomic approaches to understanding drug resistance in parasites (October, 2013).
Our understanding of the routes to drug resistance in trypanosomes, as well as our ability to dissect the modes of action of anti-trypanosomal drugs has massively increased with recent advances in high throughput approaches to functional genomics in Trypanosoma brucei, leading to the identification of more than 50 proteins contributing to the efficacy of the five anti-trypanosomal drugs (Alsford et al, 2012), including an aquaglyceroporin responsible for melarsoprol-pentamidine cross-resistance (Baker et al, 2012).
In this review, we summarise what’s known about drug resistance in trypanosomes, and the technology that has underpinned the most recent advances, whilst ackowledging past advances in understanding drug resistance in these parasites (for example: Maser et al, 1999; Wilkinson et al, 2008; Vincent et al, 2010). It also looks to the future, with the possiblilty that similar analyses using drugs against the related typanosomatid, Leishmania, will develop our understanding of drug resistance and the parasite factors that determine drug efficacy in this widespread group of parasites.
Understanding the parasite-intrinsic factors that influence drug efficacy highlights routes of drug uptake and activation, thereby identifying potential resistance mechanisms (and appropriate combination therapies to protect valuable drugs), as well as robust entry points into the parasite that we can exploit in the future.