Evidence map›Paper›PMID 26931380›Full record

ArticleScientific reports2016

A new approach to chemotherapy: drug-induced differentiation kills African trypanosomes.

Tanja Wenzler, Gabriela Schumann Burkard, Remo S Schmidt, Pascal Mäser, Andreas Bergner, Isabel Roditi, Reto Brun

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

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  11. An Overview ofFrontiers in microbiology · 2016
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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

7 authors at 3 institutions in 1 country.

Tanja WenzlerMedical Parasitology &Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Gabriela Schumann BurkardInstitute of Cell Biology, University of Bern, Bern, Switzerland.
Remo S SchmidtMedical Parasitology &Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Pascal MäserMedical Parasitology &Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Andreas BergnerBioFocus DPI, Allschwil, Switzerland.
Isabel RoditiInstitute of Cell Biology, University of Bern, Bern, Switzerland.
Reto BrunMedical Parasitology &Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel · CHUniversity of Bern · CHSwiss Tropical and Public Health Institute · CH

Funding

Howard Hughes Medical Institute 55007650
6 · The paper itself

Abstract

Human African trypanosomiasis (sleeping sickness) is a neglected tropical disease caused by Trypanosoma brucei spp. The parasites are transmitted by tsetse flies and adapt to their different hosts and environments by undergoing a series of developmental changes. During differentiation, the trypanosome alters its protein coat. Bloodstream form trypanosomes in humans have a coat of variant surface glycoprotein (VSG) that shields them from the immune system. The procyclic form, the first life-cycle stage to develop in the tsetse fly, replaces the VSG coat by procyclins; these proteins do not protect the parasite from lysis by serum components. Our study exploits the parasite-specific process of differentiation from bloodstream to procyclic forms to screen for potential drug candidates. Using transgenic trypanosomes with a reporter gene in a procyclin locus, we established a whole-cell assay for differentiation in a medium-throughput format. We screened 7,495 drug-like compounds and identified 28 hits that induced expression of the reporter and loss of VSG at concentrations in the low micromolar range. Small molecules that induce differentiation to procyclic forms could facilitate studies on the regulation of differentiation as well as serving as scaffolds for medicinal chemistry for new treatments for sleeping sickness.

Indexed as

AnimalsAnimals, Genetically ModifiedAntiprotozoal AgentsCell DifferentiationGlucuronidaseHumansProtozoan ProteinsTrypanosoma brucei bruceiVariant Surface Glycoproteins, TrypanosomaAntiprotozoal AgentsGlucuronidaseProtozoan ProteinsVariant Surface Glycoproteins, Trypanosoma

Identifiers

PMID26931380
PMCPMC4773815
OpenAlexW2292165437

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.