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. 2023 May 27;14:3059. doi: 10.1038/s41467-023-38774-1

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — A Selection scheme showing inability to evolve resistance to MMV665794 with Dd2-WT, but successful isolation of resistance with Dd2-Polδ. Upper panel: Dd2-WT exposed to 1 × IC₅₀ (95 nM) for 60 days. Lower panel: Dd2-Polδ selection pressure was ramped to 2 × IC₅₀ (190 nM), with recrudescence observed after 60 days in 3 independent flasks, but only 2 of 3 flasks could stably grow under drug pressure. Recrudescent parasites were further challenged with 3× and 4 × IC₅₀ but failed to survive. B Dose-response curves of MMV665794 for parental lines and the two resistant lines (C1-2) that were able to survive under 2 × IC₅₀ pressure. Shown is a representative assay (two technical replicates, error bars showing SD), with IC₅₀ values represented as mean values +/−SD derived from the following biological replicates (DNA-Polδ, n = 7; Polδ-R1, n = 5; Polδ-R2, n = 5). Source data are provided as a Source Data file.