Cos-Seq screening for deciphering antileishmanial drug resistance pathways and mode of action.

The emergence and spread of resistance remain a major threat in the control of neglected tropical diseases and new tools are needed for a better comprehension of resistance mechanisms for refining prevailing therapies and the development of innovative strategies. We report a sensitive method for the identification of resistance and drug target genes in Leishmania using cosmid-based enrichment coupled to next-generation sequencing, termed Cos-Seq. Cos-Seq applied to six major antileishmanials further identified more than sixty loci enriched in a drug-specific or common fashion and most of these were linked to drug resistance