Evidence map›Paper›PMID 32059044›Full record

ArticlePLoS pathogens2020

A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites.

Russell P Swift, Krithika Rajaram, Hans B Liu, Amanda Dziedzic, Anne E Jedlicka, Aleah D Roberts, Krista A Matthews, Hugo Jhun, Namandje N Bumpus, Shivendra G Tewari and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 58 citations in OpenAlex.

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  7. The therapeutic potential of atorvastatin in treatment ofFrontiers in veterinary science · 2026
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  8. Genetic analysis of pyrimidine biosynthetic enzymes inbioRxiv : the preprint server for biology · 2025
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  14. tRNA modifying enzymes MnmE and MnmG are essential forbioRxiv : the preprint server for biology · 2025
    Article
  15. Review
  16. 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 · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. A pyruvate transporter in the apicoplast of apicomplexan parasites.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Russell P SwiftDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.ORCID 0000-0003-1442-9740
Krithika RajaramDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.ORCID 0000-0003-4830-5471
Hans B LiuDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.ORCID 0000-0001-8911-5637
Amanda DziedzicDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.ORCID 0000-0002-2012-2035
Anne E JedlickaDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.ORCID 0000-0003-3826-2973
Aleah D RobertsDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.ORCID 0000-0001-6403-9236
Krista A MatthewsDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.ORCID 0000-0002-7280-2331
Hugo JhunDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.
Namandje N BumpusDepartment of Medicine (Division of Clinical Pharmacology), Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Shivendra G TewariDepartment of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Ft. Detrick, Maryland, United States of America.ORCID 0000-0003-0310-0915
Anders WallqvistDepartment of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Ft. Detrick, Maryland, United States of America.ORCID 0000-0002-9775-7469
Sean T PriggeDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.ORCID 0000-0001-9684-1733
Johns Hopkins University · USHenry M. Jackson Foundation · USTelemedicine & Advanced Technology Research Center · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
Training: Molecular & Cellular Bases of Infectious DiseasesT32AI007417 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Arturo Casadevall · 1994 to 2026
$11.9M
Determinants of apicoplast maintenance in malaria parasitesR01AI125534 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Sean Taylor PRIGGE · 2016 to 2026
$3.9M
Roles of Lipoate Pathways in Plasmodium SurvivalR01AI065853 · NIAID · JOHNS HOPKINS UNIVERSITY · PI PRIGGE, SEAN TAYLOR · 2006 to 2010
$2.0M
NCRR NIH HHS UL1 RR025005NIAID NIH HHS R01 AI065853NIAID NIH HHS R01 AI125534NIAID NIH HHS T32 AI007417
6 · The paper itself

Abstract

Malaria parasites rely on a plastid organelle for survival during the blood stages of infection. However, the entire organelle is dispensable as long as the isoprenoid precursor, isopentenyl pyrophosphate (IPP), is supplemented in the culture medium. We engineered parasites to produce isoprenoid precursors from a mevalonate-dependent pathway, creating a parasite line that replicates normally after the loss of the apicoplast organelle. We show that carbon-labeled mevalonate is specifically incorporated into isoprenoid products, opening new avenues for researching this essential class of metabolites in malaria parasites. We also show that essential apicoplast proteins, such as the enzyme target of the drug fosmidomycin, can be deleted in this mevalonate bypass parasite line, providing a new method to determine the roles of other important apicoplast-resident proteins. Several antibacterial drugs kill malaria parasites by targeting basic processes, such as transcription, in the organelle. We used metabolomic and transcriptomic methods to characterize parasite metabolism after azithromycin treatment triggered loss of the apicoplast and found that parasite metabolism and the production of apicoplast proteins is largely unaltered. These results provide insight into the effects of apicoplast-disrupting drugs, several of which have been used to treat malaria infections in humans. Overall, the mevalonate bypass system provides a way to probe essential aspects of apicoplast biology and study the effects of drugs that target apicoplast processes.

Indexed as

AnimalsAnti-Bacterial AgentsApicoplastsAzithromycinFosfomycinHemiterpenesHumansMalariaMevalonic AcidOrganophosphorus CompoundsParasitesPlasmodium falciparumPlastidsProtozoan ProteinsAnti-Bacterial AgentsAzithromycinFosfomycinfosmidomycinHemiterpenesisopentenyl pyrophosphateMevalonic AcidOrganophosphorus CompoundsProtozoan Proteins

Identifiers

PMID32059044
PMCPMC7046295
OpenAlexW3005871199

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

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.