MYST-mediated epigenetic regulation determines the adaptive artemisinin-resistant in Plasmodium falciparum [scRNA-Seq]

To investigate the artemisinin resistance mechanism, we conducted a systematical evaluation of histone acetyltransferase expression in 45 cloned P. falciparum parasites and 30 wild-type field isolates. Remarkably, PfMYST, a member of the histone acetyltransferase MYST family, emerged as the sole candidate significantly associated with prolonged ring-survive of parasites. CHIP-seq analysis revealed PfMYST’s pivotal role in mediating histone modifications, particularly in H4K5ac and H4K8ac, within the P. falciparum genome. Through single-cell RNA sequence and conditional knockdown approaches, we identified and functionally validated PfMYST-targeted genes contributing to Plasmodium’s adaptive artemisinin resistance. We conducted single-cell RNA sequencing experiments comparing wild-type and PfMYST-kd clones in response to artemisinin treatment. Single-cell transcriptomes were generated at 0, 6, and 9 h post-invasion (hpi) under 200nM artemisinin treatment for these parasites.