Abstract
In this study, in vitro drug testing was combined with proteomic and bioinformatic analyses to identify and characterize proteins involved in larval development of Oesophagostomum dentatum, an economically important parasitic nematode. Four hydrolase inhibitors ο-phenanthroline, sodium fluoride, iodoacetamide and 1,2-epoxy-3-(pnitrophenoxy)-propane (EPNP) significantly inhibited (≥90%) larval development. Comparison of the proteomic profiles of the development-inhibited larvae with those of uninhibited control larvae using two-dimensional gel electrophoresis, and subsequent MALDI-TOF mass spectrometric analysis identified a down-regulation of 12 proteins inferred to be involved in various larval developmental processes, including post-embryonic development and growth. Furthermore, three proteins (i.e. intermediate filament protein B, tropomyosin and peptidyl-prolyl cis-trans isomerase) inferred to be involved in the moulting process were down-regulated in moulting- and development-inhibited O. dentatum larvae. This first proteomic map of O. dentatum larvae provides insights in the protein profile of larval development in this parasitic nematode, and significantly improves our understanding of the fundamental biology of its development. The results and the approach used might assist in developing new interventions against parasitic nematodes by blocking or disrupting their key biological pathways.
Highlights
Parasitic roundworms of animals and humans are of major socioeconomic importance worldwide [1,2,3,4,5]
The findings of this study support the hypothesis that, in development-inhibited larvae of O. dentatum, proteins essential for developmental processes are less abundantly expressed compared with the uninhibited controls
Twelve proteins putatively involved in various larval developmental processes as well as three proteins involved in the moulting process were identified to be downregulated in the moulting- and development-inhibited O. dentatum larvae
Summary
Parasitic roundworms (nematodes) of animals and humans are of major socioeconomic importance worldwide [1,2,3,4,5]. Parasites of livestock, including species of Haemonchus, Ostertagia, Teladorsagia, Trichostrongylus and Oesophagostomum, collectively cause substantial economic losses estimated at billions of dollars per annum, due to poor productivity, failure to thrive, deaths and the cost of anthelmintic treatment [8,9,10,11]. In addition to their socioeconomic impact, widespread resistance in nematodes of livestock against the main classes of anthelmintics [12,13,14] has stimulated research toward designing alternative intervention and control strategies against these parasites. Numerous studies (reviewed in [19]) show that the porcine nodule worm, Oesophagostomum dentatum, is a unique model for studying fundamental developmental and reproductive processes in strongylid nematodes because of its short life cycle and, an ability to maintain worms in vitro for weeks through multiple moults
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