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Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets

The blood fluke Schistosoma haematobium causes urogenital schistosomiasis, a neglected tropical disease (NTD) that affects more than 110 million people. Treating this disease by targeted or mass administration with a single chemical, praziquantel, carries the risk that drug resistance will develop i...

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Autores principales: Stroehlein, Andreas J., Young, Neil D., Jex, Aaron R., Sternberg, Paul W., Tan, Patrick, Boag, Peter R., Hofmann, Andreas, Gasser, Robin B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669435/
https://www.ncbi.nlm.nih.gov/pubmed/26635209
http://dx.doi.org/10.1038/srep17759
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author Stroehlein, Andreas J.
Young, Neil D.
Jex, Aaron R.
Sternberg, Paul W.
Tan, Patrick
Boag, Peter R.
Hofmann, Andreas
Gasser, Robin B.
author_facet Stroehlein, Andreas J.
Young, Neil D.
Jex, Aaron R.
Sternberg, Paul W.
Tan, Patrick
Boag, Peter R.
Hofmann, Andreas
Gasser, Robin B.
author_sort Stroehlein, Andreas J.
collection PubMed
description The blood fluke Schistosoma haematobium causes urogenital schistosomiasis, a neglected tropical disease (NTD) that affects more than 110 million people. Treating this disease by targeted or mass administration with a single chemical, praziquantel, carries the risk that drug resistance will develop in this pathogen. Therefore, there is an imperative to search for new drug targets in S. haematobium and other schistosomes. In this regard, protein kinases have potential, given their essential roles in biological processes and as targets for drugs already approved by the US Food and Drug Administration (FDA) for use in humans. In this context, we defined here the kinome of S. haematobium using a refined bioinformatic pipeline. We classified, curated and annotated predicted kinases, and assessed the developmental transcription profiles of kinase genes. Then, we prioritised a panel of kinases as potential drug targets and inferred chemicals that bind to them using an integrated bioinformatic pipeline. Most kinases of S. haematobium are very similar to those of its congener, S. mansoni, offering the prospect of designing chemicals that kill both species. Overall, this study provides a global insight into the kinome of S. haematobium and should assist the repurposing or discovery of drugs against schistosomiasis.
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spelling pubmed-46694352015-12-09 Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets Stroehlein, Andreas J. Young, Neil D. Jex, Aaron R. Sternberg, Paul W. Tan, Patrick Boag, Peter R. Hofmann, Andreas Gasser, Robin B. Sci Rep Article The blood fluke Schistosoma haematobium causes urogenital schistosomiasis, a neglected tropical disease (NTD) that affects more than 110 million people. Treating this disease by targeted or mass administration with a single chemical, praziquantel, carries the risk that drug resistance will develop in this pathogen. Therefore, there is an imperative to search for new drug targets in S. haematobium and other schistosomes. In this regard, protein kinases have potential, given their essential roles in biological processes and as targets for drugs already approved by the US Food and Drug Administration (FDA) for use in humans. In this context, we defined here the kinome of S. haematobium using a refined bioinformatic pipeline. We classified, curated and annotated predicted kinases, and assessed the developmental transcription profiles of kinase genes. Then, we prioritised a panel of kinases as potential drug targets and inferred chemicals that bind to them using an integrated bioinformatic pipeline. Most kinases of S. haematobium are very similar to those of its congener, S. mansoni, offering the prospect of designing chemicals that kill both species. Overall, this study provides a global insight into the kinome of S. haematobium and should assist the repurposing or discovery of drugs against schistosomiasis. Nature Publishing Group 2015-12-04 /pmc/articles/PMC4669435/ /pubmed/26635209 http://dx.doi.org/10.1038/srep17759 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Stroehlein, Andreas J.
Young, Neil D.
Jex, Aaron R.
Sternberg, Paul W.
Tan, Patrick
Boag, Peter R.
Hofmann, Andreas
Gasser, Robin B.
Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets
title Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets
title_full Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets
title_fullStr Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets
title_full_unstemmed Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets
title_short Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets
title_sort defining the schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669435/
https://www.ncbi.nlm.nih.gov/pubmed/26635209
http://dx.doi.org/10.1038/srep17759
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