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

Andreas J Stroehlein,Robin B Gasser,Pasi K Korhonen,Paul W Sternberg,Andreas Hofmann,Abdul Jabbar,Neil D Young

doi:10.1186/s13071-015-1231-5

Andreas J Stroehlein, Robin B Gasser + Show 5 more

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https://doi.org/10.1186/s13071-015-1231-5

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Abstract

BackgroundProtein 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.MethodsHere, 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.ResultsWe 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 Ca2+/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.ConclusionsThe 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 materialThe online version of this article (doi:10.1186/s13071-015-1231-5) contains supplementary material, which is available to authorized users.

Highlights

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
The H. contortus kinome In total, 432 H. contortus full-length transcripts encoding protein kinases were identified, 428 (99 %) of which were detected in the draft genome
The number of kinases in the kinome of H. contortus was similar to that of C. elegans (n = 434) [44], and for most kinases (n = 409, 95 %), we detected a homolog in C. elegans, with average overall amino acid identity and similarity values of 35 % and 46 %, respectively

Summary

Introduction

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. Gaining deep insights into molecular pathways of socioeconomically important parasitic nematodes has major implications for developing new interventions against the diseases that they cause in humans, animals or plants (e.g., [7, 12, 18,19,20]), because it should be possible to define targets in these pathways for the design of new anthelmintics. Of particular significance in this context are signalling pathways, because of their crucial roles in a plethora of developmental and physiological processes Many such pathways are regulated by protein kinases, which are enzymes (transferases) that phosphorylate a substrate by transferring a phosphoryl group from an energy-rich molecule, such as adenosine triphosphate (ATP), to a target protein [27].

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