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Data · dataset · 2026

<p><i>Pf</i>ATG18-deficient ring-stage parasites are hypersensitive to dihydroartemisinin.</p>

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<p><b>(A)</b> Delayed inactivation of <i>Pf</i>ATG18 allows completion of one intraerythrocytic cycle.

Description

Parasitemia was measured after invasion and again at 68 hours post-invasion (hpi), and fold-change was calculated. DMSO or RAP was added at the indicated time points.

Dashed line: no change. Individual and mean values; paired <i>t</i>-test; n = 4 experiments with 3 technical replicates each. **, <i>p</i> < 0.01; ***, <i>p</i> < 0.001. <b>(B,C)</b> Live fluorescence microscopy shows that RAP induction at 16 hpi efficiently depletes <i>Pf</i>ATG18 (B) and causes DV fragmentation in schizonts <b>(C)</b>. Individual and mean values; paired <i>t</i>-tes<i>t</i>; n = 132 parasites, 4 experiments. <b>(D-G)</b> <i>Pf</i>ATG18 loss increases ring-stage sensitivity to dihydroartemisinin (DHA). <b>(D)</b> Experimental timeline for assessing ring-stage drug sensitivity. <i>Pf</i>ATG18 deletion was induced at 16 hpi, after which parasites completed the first intraerythrocytic cycle.

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Mature schizonts were then used to initiate a tightly synchronized (Sync) second cycle. The resulting ring stage parasites were exposed to DHA for 6 hours, and survival was assessed by Giemsa staining 16 hours later. <b>(E)</b> Representative morphologies, showing surviving and dead parasites at 24 hpi in the second cycle. <b>(F)</b> Ring-stage survival following a 6-hour DHA pulse at the indicated concentrations. <b>(G)</b> Relative ring-stage survival after a 12 nM DHA pulse, normalized to baseline survival in untreated controls. <b>(H-K)</b> <i>Pf</i>ATG18 loss does not alter ring-stage sensitivity to chloroquine (H,I) or proguanil <b>(J,K)</b>, using the same experimental time line as shown in <b>(D)</b>.

Displayed are ring-stage survival across the indicated drug concentrations (H,J) and relative ring-stage survival following a 100 nM chloroquine pulse (I) or a 100 µM proguanil pulse, normalized to baseline survival in untreated controls. Individual and mean values; paired <i>t</i>-tes<i>t</i>; n = 3 experiments with 3 technical replicates each. n.s., <i>p</i> > 0.05; *, <i>p</i> < 0.05. Scale bars: 5 µm.

Source data are provided as a <a href="plospathogens.org/article/info:doi/10.1371/journal.ppat.1014608#ppat.1014608.s015" target="_blank">S3 File</a>.</p>

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Microscopy 75%
Provenance · 1 source records, 13 field assertions
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ZivaHuboai:figshare.com:article/3401786013 d agoJSON v1
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