Functional validation of the Plasmodium falciparum K13 C580Y mutation in recently collected Ethiopian isolates

Angana Mukherjee; Ashenafi Assefa; Christopher V. Turlo; Lisa A. Checkley; Douglas A. Shoue; Tarrick Qahash; Mahlet Belachew; Dagimawie Tadesse; Enirsie Kassie; Mulu Berihun; Bokretsion Gidey Brhane; Jonathan B. Parr; Michael T. Ferdig; Sisay Adane; Adisu Tesfaye; Jenna Zuromski; Abebe Alemu Fola; Geremew Tasew; Getachew Tollera; Jonathan J. Juliano; Jeffrey A. Bailey

doi:10.1128/aac.00495-26

MicrobiologyAntimicrobial Agents and ChemotherapySep 9, 2026

Peer-reviewed journal article

Functional validation of the Plasmodium falciparum K13 C580Y mutation in recently collected Ethiopian isolates

Angana Mukherjee iD, Ashenafi Assefa iD, Christopher V. Turlo iD, Lisa A. Checkley iD, Douglas A. Shoue iD, Tarrick Qahash iD, Mahlet Belachew iD, Dagimawie Tadesse iD, Enirsie Kassie, Mulu Berihun, Bokretsion Gidey Brhane iD, Jonathan B. Parr iD, Michael T. Ferdig iD, Sisay Adane, Adisu Tesfaye iD, Jenna Zuromski iD, Abebe Alemu Fola iD, Geremew Tasew iD, Getachew Tollera iD, Jonathan J. Juliano iD, Jeffrey A. Bailey iD

Abstract

Recent genomic investigation in Ethiopia identified the first detection of the Plasmodium falciparum kelch13 (K13) C580Y substitution in the Horn of Africa. To assess its functional impact, we introduced C580Y into two recently collected Ethiopian clinical isolates using CRISPR-Cas9 genome editing. Ring-stage survival assays showed significantly elevated in vitro dihydroartemisinin (DHA) survival in edited parasites relative to isogenic controls, demonstrating that C580Y confers artemisinin tolerance in contemporary Ethiopian parasite genetic backgrounds.

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