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 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.
© 2015 Stroehlein et al. Open Access This 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. Received: 4 November 2015. Accepted: 25 November 2015. Published online: 08 December 2015. Research funding from the National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) is gratefully acknowledged. Other support from the Australian Academy of Science, the Australian-American Fulbright Commission, Alexander von Humboldt Foundation, Melbourne Water Corporation as well as the Victorian Life Sciences Computation Initiative (VLSCI) and WormBase (www.wormbase.org) is gratefully acknowledged. PWS thanks the Howard Hughes Medical Institute (HHMI) and the National Institutes of Health (NIH). AJS is a recipient of a Melbourne International Research Scholarships (MIRS) and a Melbourne International Fee Remission Scholarship (MIFRS) from the University of Melbourne. NDY is an NHMRC Early Career Research (ECR) Fellow. Authors' contributions: Conceived and designed the study and supervised the project: AJS, RBG and NDY. Undertook the study and data analysis: AJS and NDY. Contributed to analysis using various tools: NDY and PKK. Wrote the paper: AJS, NDY and RBG. Contributed to the interpretation of findings and drafting of the manuscript: AJ, AH and PWS. All authors read and approved the final version of the manuscript. The authors declare that they have no competing interests.
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