ArticlePLoS pathogens2008
A genetically hard-wired metabolic transcriptome in Plasmodium falciparum fails to mount protective responses to lethal antifolates.
Article in PLoS pathogens, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Who cites it
58 citing papers in PubMed, 158 citations in OpenAlex.
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- Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Repurposing the Pathogen Box compounds for identification of potent anti-malarials against blood stages of Plasmodium falciparum with PfUCHL3 inhibitory activity.Scientific reports · 2022Article
- Substrate-mediated regulation of the arginine transporter of Toxoplasma gondii.PLoS pathogens · 2021Article
- Article
- Transcriptome-wide dynamics of extensive mNature microbiology · 2019Article
- Plasmodium vivax transcriptomes reveal stage-specific chloroquine response and differential regulation of male and female gametocytes.Nature communications · 2019Article
- Altered expression of K13 disrupts DNA replication and repair in Plasmodium falciparum.BMC genomics · 2018Article
- Malaria Epigenetics.Cold Spring Harbor perspectives in medicine · 2017Review
- Regulation of PfEMP1-VAR2CSA translation by a Plasmodium translation-enhancing factor.Nature microbiology · 2017Article
- Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum.Scientific reports · 2017Article
- Untranslated regions of mRNA and their role in regulation of gene expression in protozoan parasites.Journal of biosciences · 2017Review
- Dynamic and Combinatorial Landscape of Histone Modifications during the Intraerythrocytic Developmental Cycle of the Malaria Parasite.Journal of proteome research · 2016Article
- Muddled mechanisms: recent progress towards antimalarial target identification.F1000Research · 2016Review
- Genome-wide transcriptome profiling reveals functional networks involving the Plasmodium falciparum drug resistance transporters PfCRT and PfMDR1.BMC genomics · 2015Article
- An integrative analysis of small molecule transcriptional responses in the human malaria parasite Plasmodium falciparum.BMC genomics · 2015Article
- Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study.BMC genomics · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Genome sequences of Plasmodium falciparum allow for global analysis of drug responses to antimalarial agents. It was of interest to learn how DNA microarrays may be used to study drug action in malaria parasites. In one large, tightly controlled study involving 123 microarray hybridizations between cDNA from isogenic drug-sensitive and drug-resistant parasites, a lethal antifolate (WR99210) failed to over-produce RNA for the genetically proven principal target, dihydrofolate reductase-thymidylate synthase (DHFR-TS). This transcriptional rigidity carried over to metabolically related RNA encoding folate and pyrimidine biosynthesis, as well as to the rest of the parasite genome. No genes were reproducibly up-regulated by more than 2-fold until 24 h after initial drug exposure, even though clonal viability decreased by 50% within 6 h. We predicted and showed that while the parasites do not mount protective transcriptional responses to antifolates in real time, P. falciparum cells transfected with human DHFR gene, and adapted to long-term WR99210 exposure, adjusted the hard-wired transcriptome itself to thrive in the presence of the drug. A system-wide incapacity for changing RNA levels in response to specific metabolic perturbations may contribute to selective vulnerabilities of Plasmodium falciparum to lethal antimetabolites. In addition, such regulation affects how DNA microarrays are used to understand the mode of action of antimetabolites.
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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.