id author title date pages extension mime words sentences flesch summary cache txt cord-103174-4m3ajc8a Okada, Megan Doxycycline has Distinct Apicoplast-Specific Mechanisms of Antimalarial Activity 2020-10-16 .txt text/plain 2809 148 49 Doxycycline (DOX) is a key antimalarial drug thought to kill Plasmodium parasites by blocking protein translation in the essential apicoplast organelle. Exogenous iron rescues parasites and apicoplast biogenesis from first-but not second-cycle effects of 10 μM DOX, revealing that first-cycle activity involves a metal-dependent mechanism distinct from the delayed-death mechanism. We observed that IPP shifted the 48-hour EC50 value of DOX from 5 ± 1 to 12 ± 2 µM 100 (average ± SD of 5 independent assays, P = 0.001 by unpaired t-test) ( Figure 2C and Figure 2 -101 figure supplement 1), suggesting that first-cycle growth defects from 5-10 µM DOX reflect an 102 apicoplast-specific mechanism but that DOX concentrations >10 µM cause off-target defects 103 outside this organelle. ./cache/cord-103174-4m3ajc8a.txt ./txt/cord-103174-4m3ajc8a.txt