Leishmania spp cause a range of devastating diseases endemic throughout the Tropics and sub-Tropics; the available drugs are limited in their efficacy and selectivity, and resistance is a developing problem (1). Apart from the roles AQP1 and an aminophospholipid translocase in the uptake of sodium stibogluconate (SSG) and miltefosine, respectively, little is known about the uptake and intracellular transit of the four anti-Leishmania drugs. Identifying these efficacy determinants will highlight potential routes to resistance, help to define the modes of action of these drugs, and has the potential to inform the development of novel interventions.
Berg M, Mannaert A, Vanaerschot M, Van Der Auwera G, Dujardin JC. (2013) (Post-) Genomic approaches to tackle drug resistance in Leishmania. Parasitology 140:1492-505
Alsford S, Horn D (2008) Single-locus targeting constructs for reliable regulated RNAi and trans-gene expression in Trypanosoma brucei. Mol Biochem Parasitol 161: 76-79
Alsford S, Turner DJ, Obado SO, Sanchez-Flores A, Glover L, Berriman M, Hertz-Fowler C, Horn D (2011) High throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome. Genome Res 21: 915-924
Alsford S, Eckert S, Baker N, Glover L, Sanchez-Flores A, Leung K, Turner DJ, Field MC, Berriman M & Horn D. (2012) High-throughput decoding of anti-trypanosomal drug efficacy and resistance. Nature 482: 232-236
Alsford S, Kelly JM, Baker N, Horn D (2013) Genetic dissection of drug resistance in trypanosomes. Parasitology 140: 1478-91