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High-throughput decoding of drug targets and drug resistance mechanisms in African trypanosomes

Published online by Cambridge University Press:  08 April 2013

DAVID HORN
DAVID HORN*
Affiliation:
London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
*
Corresponding author: London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. Tel: +44 20 7927 2352. Fax: +44 20 7636 8739. E-mail: [email protected]
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Summary

The availability of genome sequence data has facilitated the development of high-throughput genetic screening approaches in microbial pathogens. In the African trypanosome, Trypanosoma brucei, genome-scale RNA interference screens have proven particularly effective in this regard. These genetic screens allow for identification of the genes that contribute to a particular pathway or mechanisms of interest. The approach has been used to assess loss-of-fitness, revealing the genes and proteins required for parasite viability and growth. The outputs from these screens predict essential and dispensable genes and facilitate drug target prioritization efforts. The approach has also been used to assess resistance to anti-trypanosomal drugs, revealing the genes and proteins that facilitate drug uptake and action. These outputs also highlight likely mechanisms underlying clinically relevant drug resistance. I first review these findings in the context of what we know about current drugs. I then describe potential contributions that these high-throughput approaches could make to the development and implementation of new drugs.

Keywords

LeishmaniaRIT-seqRNA interferenceTrypanosoma bruceiTrypanosoma cruzi
Type
Research Article
Information
Parasitology , Volume 141 , Issue 1: Symposia of the British Society for Parasitology volume 49 Emerging paradigms in anti-infective drug design , January 2014 , pp. 77 - 82
Copyright
Copyright © Cambridge University Press 2013 

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