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#7311 : Deciphering the different molecular actors for artemisinin resistance in Plasmodium falciparum
Topics: Genomics (Illumina)
Origin: IP
Project type: Collaboration

Name of Applicant: Lise Musset
Date of application: 16-06-2022
Unit: Other
Location: Cayenne, Guyane
Phone: +594694461440
@ Mail: lise.musset@pasteur.fr
Collaboration with:FRENCH GUIANA

Project context and summary:

Artemisinins, combined with another antimalarial, are the core component of Artemisinin-based Combination Therapies (ACTs): the front-line antimalarial drugs. The fight against malaria faces to the emergence of resistance of the parasite Plasmodium falciparum to artemisinins and to its rapid and massive spread in Asia.
To understand this phenomenom and the associated molecular markers, several artemisinin-sensitive isolates, with different recrudescence capacities after artemisinins treatment, were exposed in parallel to either a selecting drug pressure using a constant pharmacological dose of 700 nM of DHA. All along the selection process, parasite culture aliquots have been collected and stored in liquid nitrogen for subsequent studies. The significant increase of parasitemia at 7 days after the drug removal (D7) means that parasites are adapting to these treatments. However, the whole genome sequencing performed shows no acquisition of non-synonymous polymorphisms previously associated with artemisinin resistance (neither in the k13 gene, nor in other candidate genes like coronin, arps10, ferredoxin, atg18, and DegP genes). Moreover, stability over time of the selected recrudescence capacities have been assessed after stopping drug pressure.
Our approach is to explore the biology of parasites under artemisinins pressure in order to identify predictive markers of the acquisition of artemisinin resistance. These evolving parasites will be characterized from a biochemical and an epigenetic point of view. The potential identified markers will be validated thanks to pharmacological and/or transgenic approaches. The most relevant markers will be searched from field isolates.


Related team publications:
Plasmodium
Artemisinins
Resistance
Service Delivery
Manager: marc.monot@pasteur.fr
Status: Closed


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