Evidence map›Paper›PMID 34737367›Full record

ArticleScientific reports2021

The transcriptome of Balamuthia mandrillaris trophozoites for structure-guided drug design.

Isabelle Q Phan, Christopher A Rice, Justin Craig, Rooksana E Noorai, Jacquelyn R McDonald, Sandhya Subramanian, Logan Tillery, Lynn K Barrett, Vijay Shankar, James C Morris and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Drug susceptibility of a clinical isolate ofAntimicrobial agents and chemotherapy · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. De Novo Transcriptome Profiling ofPathogens (Basel, Switzerland) · 2023
    Article
  9. Article
  10. Phenotypic assay for cytotoxicity assessment ofFrontiers in microbiology · 2023
    Article
  11. Review
  12. Article
  13. Review
  14. Review
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

13 authors at 5 institutions in 1 country.

Isabelle Q Phan *Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA. isabelle.phan@seattlechildrens.org.
Christopher A Rice *Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA. christopher.rice@uga.edu.
Justin CraigSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA.
Rooksana E NooraiClemson University Genomics and Bioinformatics Facility, Clemson University, Clemson, SC, USA.
Jacquelyn R McDonaldCenter for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.
Sandhya SubramanianSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA.
Logan TillerySeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA.
Lynn K BarrettSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA.
Vijay ShankarCenter for Human Genetics, Clemson University, Greenwood, SC, USA.
James C MorrisEukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson University, Clemson, SC, USA.
Wesley C Van VoorhisSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA.
Dennis E KyleCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA.
Peter J MylerSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA. peter.myler@seattlechildrens.org.
University of Washington · USClemson University · USCenter for Infectious Disease Research · USUniversity of Georgia · USInfectious Disease Research Institute · US

Funding

Regulation of Cryptosporidium DevelopmentP20GM146584 · NIGMS · CLEMSON UNIVERSITY · PI KERRY Scot SMITH · 2022 to 2026
$13.5M
The role of acetate fermentation in Entamoeba histolytica growth and infectionP20GM109094 · NIGMS · CLEMSON UNIVERSITY · PI TEMESVARI, LESLY A · 2016 to 2020
$10.4M
NIAID NIH HHS HHSN272201700059CNIGMS NIH HHS P20 GM109094NIGMS NIH HHS P20GM109094NIGMS NIH HHS P20 GM146584
6 · The paper itself

Abstract

Balamuthia mandrillaris, a pathogenic free-living amoeba, causes cutaneous skin lesions as well as granulomatous amoebic encephalitis, a 'brain-eating' disease. As with the other known pathogenic free-living amoebas (Naegleria fowleri and Acanthamoeba species), drug discovery efforts to combat Balamuthia infections of the central nervous system are sparse; few targets have been validated or characterized at the molecular level, and little is known about the biochemical pathways necessary for parasite survival. Current treatments of encephalitis due to B. mandrillaris lack efficacy, leading to case fatality rates above 90%. Using our recently published methodology to discover potential drugs against pathogenic amoebas, we screened a collection of 85 compounds with known antiparasitic activity and identified 59 compounds that impacted the growth of Balamuthia trophozoites at concentrations below 220 µM. Since there is no fully annotated genome or proteome of B. mandrillaris, we sequenced and assembled its transcriptome from a high-throughput RNA-sequencing (RNA-Seq) experiment and located the coding sequences of the genes potentially targeted by the growth inhibitors from our compound screens. We determined the sequence of 17 of these target genes and obtained expression clones for 15 that we validated by direct sequencing. These will be used in the future in combination with the identified hits in structure guided drug discovery campaigns to develop new approaches for the treatment of Balamuthia infections.

Indexed as

AcanthamoebaAmebiasisAmoebaBalamuthia mandrillarisBase SequenceBrainDrug DesignDrug DiscoveryEncephalitisGene ExpressionNaegleria fowleriTranscriptomeTrophozoites

Identifiers

PMID34737367
PMCPMC8569187
OpenAlexW3210686190

What Socratic 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 Socratic graph.