Cos-Seq for high-throughput identification of drug target and resistance mechanisms in the protozoan parasite Leishmania.

ABSTRACT: Innovative strategies are needed to accelerate the identification of antimicrobial drug targets and resistance mechanisms. Here we develop a sensitive method, which we term Cosmid Sequencing (or "Cos-Seq"), based on functional cloning coupled to next-generation sequencing. Cos-Seq identified >60 loci in the Leishmania genome that were enriched via drug selection with methotrexate and five major antileishmanials (antimony, miltefosine, paromomycin, amphotericin B, and pentamidine). Functional validation highlighted both known and previously unidentified drug targets and resistance genes, including novel roles for phosphatases in resistance to methotrexate and antimony, for ergosterol and phospholipid metabolism genes in resistance to miltefosine, and for hypothetical proteins in resistance

SUBMITTER: Gazanion E 

PROVIDER: S-EPMC4889358 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature