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High‐Throughput Decoding of Drug‐Targets and Drug‐Resistance Mechansims in African Trypanosomes
Author(s) -
Horn David
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.219.2
Subject(s) - trypanosoma brucei , suramin , biology , rna interference , drug resistance , drug , phenotype , gene , computational biology , african trypanosomiasis , genetics , trypanosoma , rna , virology , pharmacology , trypanosomiasis , receptor
High‐throughput genetic screening approaches have facilitated the decoding of a range of phenotypes in microbial pathogens. In the African trypanosomes, Trypanosoma brucei , RNA interference, coupled to deep sequencing, has proven to be particularly effective in this regard. Our RNA Interference Target sequencing, or RIT‐seq approach, was used to reveal loss‐of‐fitness phenotypes [1] and gain‐of‐fitness phenotypes in the presence of antitrypanosomal drugs [2]. This facilitates drug‐target prioritization and revealed the genes and proteins that facilitate drug action as well as those that are likely to be mutated in clinically relevant cases of resistance. In one example, suramin was shown to be taken up by receptor‐mediated endocytosis. In another, melarsoprol‐pentamidine cross‐resistance was shown to occur following loss of an aquaglyceroporin [3].