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Cos-Seq: A High-Throughput Gain-of-Function Screen for Drug Resistance Studies in Leishmania

Jade-Eva Potvin1, Philippe Leprohon1, Elodie Gazanion2

  • 1Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Centre de Recherche en Infectiologie du Centre de Recherche du CHU de Québec, Université Laval, Québec, QC, Canada.

Methods in Molecular Biology (Clifton, N.J.)
|April 14, 2019
PubMed

Insights

Leishmania parasites cause significant global health issues. A new method, Cos-Seq, aids in understanding drug resistance and developing new treatments for Leishmania infections.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Drug Discovery

Background:

  • Leishmania infections represent a significant global health burden, causing widespread mortality and morbidity.
  • Existing treatments for Leishmania are limited, and the emergence of drug resistance poses a serious threat to their efficacy.
  • A deeper understanding of drug mechanisms and resistance pathways is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To provide a detailed protocol for the Cos-Seq method, a sensitive and high-throughput technique.
  • To facilitate the identification of drug targets and mechanisms of drug resistance in Leishmania.
  • To support ongoing research in drug development and resistance studies for Leishmania.

Main Methods:

  • Detailed step-by-step protocol for Cos-Seq, including library construction and drug selection.
  • Cosmid extraction and subsequent next-generation sequencing of extracted cosmids.
  • Bioinformatic analysis tailored for Cos-Seq data.

Main Results:

  • Cos-Seq enables the identification of gain-of-function resistance mechanisms.
  • The method facilitates the discovery of novel drug targets.
  • Cos-Seq is a valuable tool for studying drug resistance and development in Leishmania.

Conclusions:

  • The Cos-Seq protocol offers a comprehensive approach for investigating Leishmania drug resistance.
  • This method enhances the understanding of how Leishmania parasites develop resistance to drugs.
  • Cos-Seq is instrumental in advancing the development of new and effective treatments against Leishmania.
Keywords:
Cos-SeqDrug resistanceLeishmaniaMode of actionNext-generation sequencing

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