AUTHOR=Sene Seynabou D. , Pouye Mariama N. , Martins Rafael Miyazawa , Diallo Fatoumata , Mangou Khadidiatou , Bei Amy K. , Barry Alioune , Faye Oumar , Ndiaye Oumar , Faye Ousmane , Sall Amadou A. , Lopez-Rubio Jose-Juan , Mbengue Alassane 

TITLE=Identification of an in vitro artemisinin-resistant Plasmodium falciparum kelch13 R515K mutant parasite in Senegal

JOURNAL=Frontiers in Parasitology

VOLUME=2

YEAR=2023

URL=https://www.frontiersin.org/journals/parasitology/articles/10.3389/fpara.2023.1076759

DOI=10.3389/fpara.2023.1076759

ISSN=2813-2424

ABSTRACT=<p>The emergence of artemisinin partial resistance (ART-r) in <italic>Plasmodium falciparum</italic> malaria parasites has substantially compromised the efficacy of antimalarial treatments across southeast Asia (SE Asia). The spread of ART-r within the African continent could jeopardize past progress made in reducing worldwide malaria burden. A clinical index malaria case was identified in Kaolack, Senegal with persistent fever after complete artesunate-amodiaquine (ASAQ) treatment. Fifteen malaria-infected blood samples were collected by Institut Pasteur Dakar’s Senegalese sentinel surveillance system, from different healthcare centers surrounding the index case. We have identified one <italic>Plasmodium falciparum</italic> clinical isolate carrying R515K mutation in the artemisinin resistance gene PfKelch13. CRISPR-Cas9 genome editing was carried out and transgenic Pf3D7Pfkelch13<sup>R515K</sup> was tested for <italic>in vitro</italic> standard Ring-stage Survival Assay <italic>(RSA</italic><sup>0-3hpi</sup>). Gene editing has confirmed that <italic>PfKelch13<sup>R515K</sup></italic> drove increased <italic>in vitro</italic> RSA<sup>0-3hpi</sup> value. In this article, we report the functional significance of PfKelch13<sup>R515K</sup> mutation in an African context.</p>