ArticleAntimicrobial agents and chemotherapy2018
Validation of Putative Apicoplast-Targeting Drugs Using a Chemical Supplementation Assay in Cultured Human Malaria Parasites.
Article in Antimicrobial agents and chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- A cytoskeleton-associated Plasmodium protein critical for organelle segregation.Nature communications · 2026Article
- Mutations in apicoplast rRNA genes are associated with clindamycin resistance and impair the ability of malaria parasites to infect mosquitoes.Antimicrobial agents and chemotherapy · 2026Article
- Acyl Carrier Protein is Essential for Apicoplast Biogenesis in Malaria Parasites Independent of Fatty Acid Synthesis.bioRxiv : the preprint server for biology · 2026Article
- An apicoplast-localized GTPase is essential formSphere · 2026Article
- Identifying antimalarials that disrupt malaria parasite transmission when fed to the mosquito.International journal for parasitology · 2025Article
- A chaperonin complex regulates organelle proteostasis in malaria parasites.PLoS pathogens · 2025Article
- Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle.Nature communications · 2025Article
- Numerous rRNA molecules form the apicomplexan mitoribosome via repurposed protein and RNA elements.Nature communications · 2025Article
- The dynamin-related protein PfDyn2 is essential for both apicoplast and mitochondrial fission inmBio · 2025Article
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- A kalihinol analog disrupts apicoplast function and vesicular trafficking inScience (New York, N.Y.) · 2024Article
- Apicoplast-Resident Processes: Exploiting the Chink in the Armour ofAdvances in pharmacological and pharmaceutical sciences · 2024Review
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- A High-Throughput Amenable Dual Luciferase System for MeasuringAnalytical chemistry · 2023Article
- Roles of the apicoplast across the life cycles of rodent and human malaria parasites.The Journal of eukaryotic microbiology · 2022Review
- Targeting theHeliyon · 2022Review
- Article
- Artemisinin-independent inhibitory activity ofLife science alliance · 2022Article
- Targeting malaria parasites with novel derivatives of azithromycin.Frontiers in cellular and infection microbiology · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malaria parasites contain a relict plastid, the apicoplast, which is considered an excellent drug target due to its bacterial-like ancestry. Numerous parasiticidals have been proposed to target the apicoplast, but few have had their actual targets substantiated. Isopentenyl pyrophosphate (IPP) production is the sole required function of the apicoplast in the blood stage of the parasite life cycle, and IPP supplementation rescues parasites from apicoplast-perturbing drugs. Hence, any drug that kills parasites when IPP is supplied in culture must have a nonapicoplast target. Here, we use IPP supplementation to discriminate whether 23 purported apicoplast-targeting drugs are on- or off-target. We demonstrate that a prokaryotic DNA replication inhibitor (ciprofloxacin), several prokaryotic translation inhibitors (chloramphenicol, doxycycline, tetracycline, clindamycin, azithromycin, erythromycin, and clarithromycin), a tRNA synthase inhibitor (mupirocin), and two IPP synthesis pathway inhibitors (fosmidomycin and FR900098) have apicoplast targets. Intriguingly, fosmidomycin and FR900098 leave the apicoplast intact, whereas the others eventually result in apicoplast loss. Actinonin, an inhibitor of bacterial posttranslational modification, does not produce a typical delayed-death response but is rescued with IPP, thereby confirming its apicoplast target. Parasites treated with putative apicoplast fatty acid pathway inhibitors could not be rescued, demonstrating that these drugs have their primary targets outside the apicoplast, which agrees with the dispensability of the apicoplast fatty acid synthesis pathways in the blood stage of malaria parasites. IPP supplementation provides a simple test of whether a compound has a target in the apicoplast and can be used to screen novel compounds for mode of action.
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