ArticleAntimicrobial agents and chemotherapy2006
Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.
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Who cites it
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 267 citations in OpenAlex.
- Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis.The American journal of tropical medicine and hygiene · 2011Guideline
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- Tetracyclines, a timely resurgence or doomed to fail again?Journal of medical microbiology · 2026Review
- Discovery of Sphaeriaurantins as Rapid-Acting Antiplasmodials with Dual Activity in Blood and Liver Stages.Journal of the American Chemical Society · 2026Article
- Article
- Repositioning Antibiotics Against Plasmodium falciparum RAD5 and WD11 as Novel Antimalarial Targets.Tropical medicine & international health : TM & IH · 2026Article
- Identification of a Putative Metal Transporter in the Apicoplast of Malaria Parasites.bioRxiv : the preprint server for biology · 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 essential adaptor for apicoplast fission and inheritance in malaria parasites.Nature communications · 2025Article
- Toxicity assessment of doxycycline-aided artificial intelligence-assisted drug design targeting candidate 16S rRNA methyltransferase gene.BMC pharmacology & toxicology · 2025Article
- An Essential Adaptor for Apicoplast Fission and Inheritance in Malaria Parasites.bioRxiv : the preprint server for biology · 2025Article
- A review of natural products as a source of next-generation drugs against apicomplexan parasites.npj antimicrobials and resistance · 2025Review
- Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis.eLife · 2024Article
- Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis.bioRxiv : the preprint server for biology · 2024Article
- Real-time measurements of ATP dynamics via ATeams inAntimicrobial agents and chemotherapy · 2024Article
- Successful treatment with doxycycline monotherapy for human infection with Babesia venatorum (Babesiidae, Sporozoa) in China: a case report and proposal for a clinical regimen.Infectious diseases of poverty · 2023Article
- Novel Therapeutics for Malaria.Pharmaceutics · 2023Review
- Magic bullets, magic shields, and antimicrobials in between.Pharmaceutical science advances · 2023Review
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- Protein kinases on carbon metabolism: potential targets for alternative chemotherapies against toxoplasmosis.Frontiers in cellular and infection microbiology · 2023Review
59 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Tetracyclines are effective but slow-acting antimalarial drugs whose mechanism of action remains uncertain. To characterize the antimalarial mechanism of tetracyclines, we evaluated their stage-specific activities, impacts on parasite transcription, and effects on two predicted organelle targets, the apicoplast and the mitochondrion, in cultured Plasmodium falciparum. Antimalarial effects were much greater after two 48-h life cycles than after one cycle, even if the drugs were removed at the end of the first cycle. Doxycycline-treated parasites appeared morphologically normal until late in the second cycle of treatment but failed to develop into merozoites. Doxycycline specifically impaired the expression of apicoplast genes. Apicoplast morphology initially appeared normal in the presence of doxycycline. However, apicoplasts were abnormal in the progeny of doxycycline-treated parasites, as evidenced by a block in apicoplast genome replication, a lack of processing of an apicoplast-targeted protein, and failure to elongate and segregate during schizogeny. Replication of the nuclear and mitochondrial genomes and mitochondrial morphology appeared normal. Our results demonstrate that tetracyclines specifically block expression of the apicoplast genome, resulting in the distribution of nonfunctional apicoplasts into daughter merozoites. The loss of apicoplast function in the progeny of treated parasites leads to a slow but potent antimalarial effect.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.