Evidence map›Paper›PMID 36788578›Full record

ArticleMalaria journal2023

Metabolic responses in blood-stage malaria parasites associated with increased and decreased sensitivity to PfATP4 inhibitors.

Shivendra G Tewari, Rubayet Elahi, Bobby Kwan, Krithika Rajaram, Suyash Bhatnagar, Jaques Reifman, Sean T Prigge, Akhil B Vaidya, Anders Wallqvist

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Malaria journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. 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

9 authors at 5 institutions in 1 country.

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, Fort Detrick, MD, USA. stewari@bhsai.org.
Rubayet ElahiDepartment of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD, USA.
Bobby KwanDepartment of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD, USA.
Krithika RajaramDepartment of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD, USA.
Suyash BhatnagarCenter for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
Jaques ReifmanDepartment of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, MD, USA.
Sean T PriggeDepartment of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD, USA.
Akhil B VaidyaCenter for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
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, Fort Detrick, MD, USA. sven.a.wallqvist.civ@health.mil.
Johns Hopkins University · USTelemedicine & Advanced Technology Research Center · USCenter for Biologics Evaluation and Research · USDrexel University · USHenry M. Jackson Foundation · US

Funding

Molecular Pathways Affected by Drugs that Disrupt Na+ Homeostasis in Malaria ParasitesR01AI132508 · NIAID · DREXEL UNIVERSITY · PI AKHIL B VAIDYA · 2017 to 2026
$5.7M
Determinants of apicoplast maintenance in malaria parasitesR01AI125534 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Sean Taylor PRIGGE · 2016 to 2026
$3.9M
Malaria and Mosquito/Tick-borne DiseasesT32AI138953 · NIAID · JOHNS HOPKINS UNIVERSITY · PI DAVID Joseph SULLIVAN · 2019 to 2026
$2.0M
Molecular Pathways Targeted by Potent Antimalarial Pyrazole CompoundsR01AI098413 · NIAID · DREXEL UNIVERSITY · PI VAIDYA, AKHIL B · 2012 to 2015
$1.9M
NIAID NIH HHS R01 AI098413NIAID NIH HHS R01 AI125534NIAID NIH HHS R01 AI132508NIAID NIH HHS T32 AI138953U.S. Army Medical Research and Development Command W81XWH-14-2-0134U.S. Army Medical Research and Development Command W81XWH-15-C-0061
6 · The paper itself

Abstract

backgroundSpiroindolone and pyrazoleamide antimalarial compounds target Plasmodium falciparum P-type ATPase (PfATP4) and induce disruption of intracellular Na

methodsA genetically engineered P. falciparum Dd2 strain (Dd2

resultsSublethal treatment with PA21A092 caused significant (p < 0.001) alterations in the abundances of 91 Plasmodium gene transcripts, whereas only 21 transcripts were significantly altered due to sublethal treatment with KAE609. In the metabolomic data, a substantial alteration (≥ fourfold) in the abundances of carbohydrate metabolites in the presence of either compound was found. The estimated rates of macromolecule syntheses between the two antimalarial-treated conditions were also comparable, except for the rate of lipid synthesis. A closer examination of parasite metabolism in the presence of either compound indicated statistically significant differences in enzymatic activities associated with synthesis of phosphatidylcholine, phosphatidylserine, and phosphatidylinositol.

conclusionThe results of this study suggest that malaria parasites activate protein kinases via phospholipid-dependent signalling in response to the ionic perturbation induced by the Na

Indexed as

AntimalarialsMalariaMalaria, FalciparumParasitesAnimalsIndolesPhospholipidsPlasmodium falciparumSpiro CompoundsAntimalarialsIndolesNITD 609PhospholipidsSpiro CompoundsDrug resistanceGenome-scale metabolic network modelMetabolomicsNa+ homeostasisPlasmodium falciparumTranscriptomics

Identifiers

PMID36788578
PMCPMC9930341
OpenAlexW4320856297

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.