Cargando…

The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery

BACKGROUND: Protein kinases regulate a plethora of essential signalling and other biological pathways in all eukaryotic organisms, but very little is known about them in most parasitic nematodes. METHODS: Here, we defined, for the first time, the entire complement of protein kinases (kinome) encoded...

Descripción completa

Detalles Bibliográficos
Autores principales: Stroehlein, Andreas J., Young, Neil D., Korhonen, Pasi K., Jabbar, Abdul, Hofmann, Andreas, Sternberg, Paul W., Gasser, Robin B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672506/
https://www.ncbi.nlm.nih.gov/pubmed/26644012
http://dx.doi.org/10.1186/s13071-015-1231-5
_version_ 1782404581409423360
author Stroehlein, Andreas J.
Young, Neil D.
Korhonen, Pasi K.
Jabbar, Abdul
Hofmann, Andreas
Sternberg, Paul W.
Gasser, Robin B.
author_facet Stroehlein, Andreas J.
Young, Neil D.
Korhonen, Pasi K.
Jabbar, Abdul
Hofmann, Andreas
Sternberg, Paul W.
Gasser, Robin B.
author_sort Stroehlein, Andreas J.
collection PubMed
description BACKGROUND: Protein kinases regulate a plethora of essential signalling and other biological pathways in all eukaryotic organisms, but very little is known about them in most parasitic nematodes. METHODS: Here, we defined, for the first time, the entire complement of protein kinases (kinome) encoded in the barber’s pole worm (Haemonchus contortus) through an integrated analysis of transcriptomic and genomic datasets using an advanced bioinformatic workflow. RESULTS: We identified, curated and classified 432 kinases representing ten groups, 103 distinct families and 98 subfamilies. A comparison of the kinomes of H. contortus and Caenorhabditis elegans (a related, free-living nematode) revealed considerable variation in the numbers of casein kinases, tyrosine kinases and Ca(2+)/calmodulin-dependent protein kinases, which likely relate to differences in biology, habitat and life cycle between these worms. Moreover, a suite of kinase genes was selectively transcribed in particular developmental stages of H. contortus, indicating central roles in developmental and reproductive processes. In addition, using a ranking system, drug targets (n = 13) and associated small-molecule effectors (n = 1517) were inferred. CONCLUSIONS: The H. contortus kinome will provide a useful resource for fundamental investigations of kinases and signalling pathways in this nematode, and should assist future anthelmintic discovery efforts; this is particularly important, given current drug resistance problems in parasitic nematodes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1231-5) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4672506
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-46725062015-12-09 The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery Stroehlein, Andreas J. Young, Neil D. Korhonen, Pasi K. Jabbar, Abdul Hofmann, Andreas Sternberg, Paul W. Gasser, Robin B. Parasit Vectors Research BACKGROUND: Protein kinases regulate a plethora of essential signalling and other biological pathways in all eukaryotic organisms, but very little is known about them in most parasitic nematodes. METHODS: Here, we defined, for the first time, the entire complement of protein kinases (kinome) encoded in the barber’s pole worm (Haemonchus contortus) through an integrated analysis of transcriptomic and genomic datasets using an advanced bioinformatic workflow. RESULTS: We identified, curated and classified 432 kinases representing ten groups, 103 distinct families and 98 subfamilies. A comparison of the kinomes of H. contortus and Caenorhabditis elegans (a related, free-living nematode) revealed considerable variation in the numbers of casein kinases, tyrosine kinases and Ca(2+)/calmodulin-dependent protein kinases, which likely relate to differences in biology, habitat and life cycle between these worms. Moreover, a suite of kinase genes was selectively transcribed in particular developmental stages of H. contortus, indicating central roles in developmental and reproductive processes. In addition, using a ranking system, drug targets (n = 13) and associated small-molecule effectors (n = 1517) were inferred. CONCLUSIONS: The H. contortus kinome will provide a useful resource for fundamental investigations of kinases and signalling pathways in this nematode, and should assist future anthelmintic discovery efforts; this is particularly important, given current drug resistance problems in parasitic nematodes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1231-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-08 /pmc/articles/PMC4672506/ /pubmed/26644012 http://dx.doi.org/10.1186/s13071-015-1231-5 Text en © Stroehlein et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Stroehlein, Andreas J.
Young, Neil D.
Korhonen, Pasi K.
Jabbar, Abdul
Hofmann, Andreas
Sternberg, Paul W.
Gasser, Robin B.
The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery
title The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery
title_full The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery
title_fullStr The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery
title_full_unstemmed The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery
title_short The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery
title_sort haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672506/
https://www.ncbi.nlm.nih.gov/pubmed/26644012
http://dx.doi.org/10.1186/s13071-015-1231-5
work_keys_str_mv AT stroehleinandreasj thehaemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT youngneild thehaemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT korhonenpasik thehaemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT jabbarabdul thehaemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT hofmannandreas thehaemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT sternbergpaulw thehaemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT gasserrobinb thehaemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT stroehleinandreasj haemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT youngneild haemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT korhonenpasik haemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT jabbarabdul haemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT hofmannandreas haemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT sternbergpaulw haemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery
AT gasserrobinb haemonchuscontortuskinomearesourceforfundamentalmolecularinvestigationsanddrugdiscovery