ArticleThe Journal of biological chemistry2009
Co-inhibition of Plasmodium falciparum S-adenosylmethionine decarboxylase/ornithine decarboxylase reveals perturbation-specific compensatory mechanisms by transcriptome, proteome, and metabolome analyses.
Article in The Journal of biological chemistry, 2009. 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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Who cites it
40 citing papers in PubMed, 79 citations in OpenAlex.
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- A Candidate Bacterial-Type Amino Acid Decarboxylase Is Essential for Male Gamete Exflagellation and Mosquito Transmission of the Malaria Parasite.Infection and immunity · 2023Article
- The human malaria parasiteProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cripowellins PauseMolecules (Basel, Switzerland) · 2023Article
- A non-canonical sensing pathway mediates Plasmodium adaptation to amino acid deficiency.Communications biology · 2023Article
- An Undefined Interaction between Polyamines and Heat Shock Proteins Leads to Cellular Protection inMolecules (Basel, Switzerland) · 2023Review
- Current and emerging target identification methods for novel antimalarials.International journal for parasitology. Drugs and drug resistance · 2022Review
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- Machine Learning Uses Chemo-Transcriptomic Profiles to Stratify Antimalarial Compounds With Similar Mode of Action.Frontiers in cellular and infection microbiology · 2021Article
- 6'-β-Fluoro-Homoaristeromycin and 6'-Fluoro-Homoneplanocin A Are Potent Inhibitors of Chikungunya Virus Replication through Their Direct Effect on Viral Nonstructural Protein 1.Antimicrobial agents and chemotherapy · 2020Article
- Novel Synthetic Polyamines Have Potent Antimalarial ActivitiesFrontiers in cellular and infection microbiology · 2019Article
- Polyamines in protozoan pathogens.The Journal of biological chemistry · 2018Review
- Inducing controlled cell cycle arrest and re-entry during asexual proliferation of Plasmodium falciparum malaria parasites.Scientific reports · 2018Article
- The roles of polyamines in microorganisms.World journal of microbiology & biotechnology · 2017Review
- Simultaneous genome-wide gene expression and transcript isoform profiling in the human malaria parasite.PloS one · 2017Article
- Metabolomics-Based Screening of the Malaria Box Reveals both Novel and Established Mechanisms of Action.Antimicrobial agents and chemotherapy · 2016Article
- Signaling transcript profile of the asexual intraerythrocytic development cycle ofGenes & cancer · 2016Article
- Muddled mechanisms: recent progress towards antimalarial target identification.F1000Research · 2016Review
- An integrative analysis of small molecule transcriptional responses in the human malaria parasite Plasmodium falciparum.BMC genomics · 2015Article
- Screening of potential targets in Plasmodium falciparum using stage-specific metabolic network analysis.Molecular diversity · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Polyamines are ubiquitous components of all living cells, and their depletion usually causes cytostasis, a strategy employed for treatment of West African trypanosomiasis. To evaluate polyamine depletion as an anti-malarial strategy, cytostasis caused by the co-inhibition of S-adenosylmethionine decarboxylase/ornithine decarboxylase in Plasmodium falciparum was studied with a comprehensive transcriptome, proteome, and metabolome investigation. Highly synchronized cultures were sampled just before and during cytostasis, and a novel zero time point definition was used to enable interpretation of results in lieu of the developmentally regulated control of gene expression in P. falciparum. Transcriptome analysis revealed the occurrence of a generalized transcriptional arrest just prior to the growth arrest due to polyamine depletion. However, the abundance of 538 transcripts was differentially affected and included three perturbation-specific compensatory transcriptional responses as follows: the increased abundance of the transcripts for lysine decarboxylase and ornithine aminotransferase and the decreased abundance of that for S-adenosylmethionine synthetase. Moreover, the latter two compensatory mechanisms were confirmed on both protein and metabolite levels confirming their biological relevance. In contrast with previous reports, the results provide evidence that P. falciparum responds to alleviate the detrimental effects of polyamine depletion via regulation of its transcriptome and subsequently the proteome and metabolome.
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Registered trials
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.