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

Stroehlein, Andreas J. and Young, Neil D. and Jex, Aaron R. and Sternberg, Paul W. and Tan, Patrick and Boag, Peter R. and Hofmann, Andreas and Gasser, Robin B. (2015) Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets. Scientific Reports, 5 . Art. No. 17759. ISSN 2045-2322. PMCID PMC4669435. https://resolver.caltech.edu/CaltechAUTHORS:20151215-155916318

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/srep17759DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669435/PubMed CentralArticle
ORCID:
AuthorORCID
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 2015 Macmillan Publishers Limited. 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/ Received: 06 May 2015; Accepted: 26 August 2015; Published online: 04 December 2015. TThis project was funded by the National Health and Medical Research Council (NHMRC) of Australia and the Australian Research Council (ARC), and supported by a Victorian Life Sciences Computation Initiative (VLSCI) grant number VR0007 on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government. Other support from the Australian Academy of Science, the Australian-American Fulbright Commission, Alexander von Humboldt Foundation and Melbourne Water Corporation (R.B.G.) is gratefully acknowledged. A.J.S. is a recipient of a Melbourne International Research Scholarships (MIRS) and a Melbourne International Fee Remission Scholarship (MIFRS) from the University of Melbourne. N.D.Y. is an NHMRC Early Career Research (ECR) Fellow. We thank Stefano Mangiola for help with preliminary data analysis. Author Contributions: A.J.S., R.B.G. and N.D.Y. were involved in the experimental design. A.J.S., R.B.G. and N.D.Y. were responsible for writing and editing of the manuscript. A.J.S. and N.D.Y. conducted bioinformatic analyses. Other authors (A.R.J., P.W.S., P.T., P.R.B. and A.H.) contributed to the writing of the manuscript. The authors declare no competing financial interests.
Funders:
Funding AgencyGrant Number
National Health and Medical Research Council (NHMRC)UNSPECIFIED
Australian Research CouncilUNSPECIFIED
Victorian Life Sciences Computation Initiative (VLSCI)VR0007
Australian Academy of ScienceUNSPECIFIED
Australian-American Fulbright CommissionUNSPECIFIED
Alexander von Humboldt FoundationUNSPECIFIED
Melbourne Water CorporationUNSPECIFIED
University of MelbourneUNSPECIFIED
PubMed Central ID:PMC4669435
Record Number:CaltechAUTHORS:20151215-155916318
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20151215-155916318
Official Citation:Stroehlein, A. J. et al. Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets. Sci. Rep. 5, 17759; doi: 10.1038/srep17759 (2015).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:62957
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:16 Dec 2015 00:44
Last Modified:03 Oct 2019 09:23

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