Evidence map›Paper›PMID 24533291›Full record

ArticleInternational journal for parasitology. Drugs and drug resistance2013

Identification of differentially expressed proteins in sulfadiazine resistant and sensitive strains of Toxoplasma gondii using difference-gel electrophoresis (DIGE).

Christelle Doliwa, Dong Xia, Sandie Escotte-Binet, Emma L Newsham, Sanderson Sanya J, Dominique Aubert, Nadine Randle, Jonathan M Wastling, Isabelle Villena

Open access · goldAbstract read
In one paragraph

Article in International journal for parasitology. Drugs and drug resistance, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 11% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  14. Mining the Proteome ofAnimals : an open access journal from MDPI · 2022
    Review
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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

9 authors at 3 institutions in 2 countries.

Christelle DoliwaProtozooses, transmises par l'alimentation: circulation et pathogénie, EA 3800, SFR CAP-Santé FED 4231, Université de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, 51095 Reims Cedex, France.
Dong XiaInstitute of Infection & Global Health, Faculty of Health and Life Sciences, University of Liverpool, Brownlow Hill, Liverpool L69 7ZJ, United Kingdom.
Sandie Escotte-BinetProtozooses, transmises par l'alimentation: circulation et pathogénie, EA 3800, SFR CAP-Santé FED 4231, Université de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, 51095 Reims Cedex, France ; BRC Toxoplasma and NRC on Toxoplasmosis, Hôpital Maison Blanche, 45 rue Cognacq-Jay, 51092 Reims Cedex, France.
Emma L NewshamInstitute of Infection & Global Health, Faculty of Health and Life Sciences, University of Liverpool, Brownlow Hill, Liverpool L69 7ZJ, United Kingdom.
Sanderson Sanya JInstitute of Infection & Global Health, Faculty of Health and Life Sciences, University of Liverpool, Brownlow Hill, Liverpool L69 7ZJ, United Kingdom.
Dominique AubertProtozooses, transmises par l'alimentation: circulation et pathogénie, EA 3800, SFR CAP-Santé FED 4231, Université de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, 51095 Reims Cedex, France ; BRC Toxoplasma and NRC on Toxoplasmosis, Hôpital Maison Blanche, 45 rue Cognacq-Jay, 51092 Reims Cedex, France.
Nadine RandleInstitute of Infection & Global Health, Faculty of Health and Life Sciences, University of Liverpool, Brownlow Hill, Liverpool L69 7ZJ, United Kingdom.
Jonathan M WastlingInstitute of Infection & Global Health, Faculty of Health and Life Sciences, University of Liverpool, Brownlow Hill, Liverpool L69 7ZJ, United Kingdom.
Isabelle VillenaProtozooses, transmises par l'alimentation: circulation et pathogénie, EA 3800, SFR CAP-Santé FED 4231, Université de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, 51095 Reims Cedex, France ; BRC Toxoplasma and NRC on Toxoplasmosis, Hôpital Maison Blanche, 45 rue Cognacq-Jay, 51092 Reims Cedex, France.
University of Liverpool · GBHôpital Maison Blanche · FRUniversité de Reims Champagne-Ardenne · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Treatment options for toxoplasmosis in humans are generally limited to the use of sulfonamide and/or pyrimethamine-based compounds. However, there is increasing evidence for clinical therapy failures in patients suggesting the existence of drug resistance in these classes of drug. In vitro resistance to sulfadiazine has been detected in three strains of Toxoplasma gondii isolated from clinical cases. In order to begin to understand the mechanisms of resistance, we undertook a difference-gel electrophoresis (DIGE) approach combined with mass spectrometry to identify proteins that are differentially expressed in sulfadiazine-resistance strains of the parasite. Naturally resistant strains TgA 103001 (Type I), TgH 32006 (Type II) and TgH 32045 (Type II variant) were compared to sensitive strains RH (Type I) and ME-49 (Type II) using DIGE and the modulated proteins analyzed using LC-MS/MS. In total, 68 differentially expressed protein spots were analyzed by mass spectrometer and 31 unique proteins, including four hypothetical proteins, were identified. Among the differentially expressed proteins, 44% were over-expressed in resistant strains and 56% were over-expressed in sensitive strains. The virulence-associated rhoptry protein, ROP2A, was found in greater abundance in both naturally resistant Type II strains TgH 32006 and TgH 32045 compared to the sensitive strain ME-49. Enolase 2 and IMC1 were found to be in greater abundance in sensitive strains RH and ME-49, and MIC2 was found to be more abundant in the sensitive strain ME-49. Proteins regulation of ROP2, MIC2, ENO2, IMC1 and GRA7 were confirmed by Western blot analysis. In addition, gene expression patterns of ROP2, MIC2, ENO2 and IMC1 were analyzed with qRT-PCR. This study provides the first proteomics insights into sulfadiazine resistance in T. gondii resistant strains isolated from clinical cases.

Indexed as

DIGEDrug resistanceEF1-α, elongation factor 1 alphaeIF-5A, translation initiation factor 5AENO2, enolase 2G3PDH, glyceraldehyde-3-phosphate dehydrogenaseGRA2, dense granule protein 2GRA7, dense granule protein 7Hsp70, heat shock protein 70Hsp90, heat shock protein 90MIC1, microneme protein 1MIC2, microneme protein 2PP2C, protein phosphatase 2CROP2, rhoptry protein 2ROP9, rhoptry protein 9small Hsp20, small heat shock protein 20SulfadiazineTgCDPK1, Toxoplasma gondii calcium-dependent protein kinase 1Toxoplasma gondii

Identifiers

PMID24533291
PMCPMC3862439
OpenAlexW1975729254

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Registered trials

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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.