Veterinary Biosciences - Research Publications
Permanent URI for this collection
Search Results
1 - 8 of 8
-
ItemProteomic analysis of Sarcoptes scabiei reveals that proteins differentially expressed between eggs and female adult stages are involved predominantly in genetic information processing, metabolism and/or host-parasite interactions(PUBLIC LIBRARY SCIENCE, 2022-12)Presently, there is a dearth of proteomic data for parasitic mites and their relationship with the host animals. Here, using a high throughput LC-MS/MS-based approach, we undertook the first comprehensive, large-scale proteomic investigation of egg and adult female stages of the scabies mite, Sarcoptes scabiei-one of the most important parasitic mites of humans and other animals worldwide. In total, 1,761 S. scabiei proteins were identified and quantified with high confidence. Bioinformatic analyses revealed differentially expressed proteins to be involved predominantly in biological pathways or processes including genetic information processing, energy (oxidative phosphorylation), nucleotide, amino acid, carbohydrate and/or lipid metabolism, and some adaptive processes. Selected, constitutively and highly expressed proteins, such as peptidases, scabies mite inactivated protease paralogues (SMIPPs) and muscle proteins (myosin and troponin), are proposed to be involved in key biological processes within S. scabiei, host-parasite interactions and/or the pathogenesis of scabies. These proteomic data will enable future molecular, biochemical and physiological investigations of early developmental stages of S. scabiei and the discovery of novel interventions, targeting the egg stage, given its non-susceptibility to acaricides currently approved for the treatment of scabies in humans.
-
ItemNo Preview AvailableUbiquitination pathway model for the barber's pole worm - Haemonchus contortus(ELSEVIER SCI LTD, 2022-08)The ubiquitin-mediated pathway has been comprehensively explored in the free-living nematode Caenorhabditis elegans, but very little is known about this pathway in parasitic nematodes. Here, we inferred the ubiquitination pathway for an economically significant and pathogenic nematode - Haemonchus contortus - using abundant resources available for C. elegans. We identified 215 genes encoding ubiquitin (Ub; n = 3 genes), ubiquitin-activating enzyme (E1; one), -conjugating enzymes (E2s; 21), ligases (E3s; 157) and deubiquitinating enzymes (DUBs; 33). With reference to C. elegans, Ub, E1 and E2 were relatively conserved in sequence and structure, and E3s and DUBs were divergent, likely reflecting functional and biological uniqueness in H. contortus. Most genes encoding ubiquitination pathway components exhibit high transcription in the egg compared with other stages, indicating marked protein homeostasis in this early developmental stage. The ubiquitination pathway model constructed for H. contortus provides a foundation to explore the ubiquitin-proteasome system, crosstalk between autophagy and the proteasome system, and the parasite-host interactions. Selected E3 and DUB proteins which are very divergent in sequence and structure from host homologues or entirely unique to H. contortus and related parasitic nematodes may represent possible anthelmintic targets.
-
ItemEvidence that Transcriptional Alterations in Sarcoptes scabiei Are under Tight Post-Transcriptional (microRNA) Control(MDPI, 2022-09)Here, we explored transcriptomic differences among early egg (Ee), late egg (Le) and adult female (Af) stages of the scabies mite, Sarcoptes scabiei, using an integrative bioinformatic approach. We recorded a high, negative correlation between miRNAs and genes with decreased mRNA transcription between the developmental stages, indicating substantial post-transcriptional repression; we also showed a positive correlation between miRNAs and genes with increased mRNA transcription, suggesting indirect post-transcriptional regulation. The alterations in mRNA transcription between the egg and adult female stages of S. scabiei were inferred to be linked to metabolism (including carbohydrate and lipid degradation, amino acid and energy metabolism), environmental information processing (e.g., signal transduction and signalling molecules), genetic information processing (e.g., transcription and translation) and/or organismal systems. Taken together, these results provide insight into the transcription of this socioeconomically important parasitic mite, with a particular focus on the egg stage. This work encourages further, detailed laboratory studies of miRNA regulation across all developmental stages of S. scabiei and might assist in discovering new intervention targets in the egg stage of S. scabiei.
-
ItemRepurposing of a human antibody-based microarray to explore conserved components of the signalome of the parasitic nematode Haemonchus contortus(BMC, 2022-07-30)BACKGROUND: Gaining insight into molecular signalling pathways of socioeconomically important parasitic nematodes has implications for understanding their molecular biology and for developing novel anthelmintic interventions. METHODS: Here, we evaluated the use of a human antibody-based microarray to explore conserved elements of the signalome in the barber's pole worm Haemonchus contortus. To do this, we prepared extracts from mixed-sex (female and male) adult worms and third-stage larvae (L3s), incubated these extracts on the antibody microarray and then measured the amounts of antibody-bound proteins ('signal intensity'). RESULTS: In total, 878 signals were classified into two distinct categories: signals that were higher for adults than for larvae of H. contortus (n = 376), and signals that were higher for larvae than for adults of this species (n = 502). Following a data-filtering step, high confidence ('specific') signals were obtained for subsequent analyses. In total, 39 pan-specific signals (linked to antibodies that recognise target proteins irrespective of their phosphorylation status) and 65 phosphorylation-specific signals were higher in the adult stage, and 82 pan-specific signals and 183 phosphorylation-specific signals were higher in L3s. Thus, notably more signals were higher in L3s than in the adult worms. Using publicly available information, we then inferred H. contortus proteins that were detected (with high confidence) by specific antibodies directed against human homologues, and revealed relatively high structural conservation between the two species, with some variability for select proteins. We also in silico-matched 763 compound structures (listed in the DrugBank and Kinase SARfari public databases) to four H. contortus proteins (designated HCON_00005760, HCON_00079680, HCON_00013590 and HCON_00105100). CONCLUSIONS: We conclude that the present antibody-based microarray provides a useful tool for comparative analyses of signalling pathways between/among developmental stages and/or species, as well as opportunities to explore nematocidal target candidates in H. contortus and related parasites.
-
ItemComparative bioinformatic analysis suggests that specific dauer-like signalling pathway components regulate Toxocara canis development and migration in the mammalian host(BMC, 2019-01-14)BACKGROUND: Toxocara canis is quite closely related to Ascaris suum but its biology is more complex, involving a phase of arrested development (diapause or hypobiosis) in tissues as well as transplacental and transmammary transmission routes. In the present study, we explored and compared dauer-like signalling pathways of T. canis and A. suum to infer which components in these pathways might associate with, or regulate, this added complexity in T. canis. METHODS: Guided by information for Caenorhabditis elegans, we bioinformatically inferred and compared components of dauer-like signalling pathways in T. canis and A. suum using genomic and transcriptomic data sets. In these two ascaridoids, we also explored endogenous dafachronic acids (DAs), which are known to be critical in regulating larval developmental processes in C. elegans and other nematodes, by liquid chromatography-mass spectrometry (LC-MS). RESULTS: Orthologues of C. elegans dauer signalling genes were identified in T. canis (n = 55) and A. suum (n = 51), inferring the presence of a dauer-like signalling pathway in both species. Comparisons showed clear differences between C. elegans and these ascaridoids as well as between T. canis and A. suum, particularly in the transforming growth factor-β (TGF-β) and insulin-like signalling pathways. Specifically, in both A. suum and T. canis, there was a paucity of genes encoding SMAD transcription factor-related protein (daf-3, daf-5, daf-8 and daf-14) and insulin/insulin-like peptide (daf-28, ins-4, ins-6 and ins-7) homologues, suggesting an evolution and adaptation of the signalling pathway in these parasites. In T. canis, there were more orthologues coding for homologues of antagonist insulin-like peptides (Tc-ins-1 and Tc-ins-18), an insulin receptor substrate (Tc-ist-1) and a serine/threonine kinase (Tc-akt-1) than in A. suum, suggesting potentiated functional roles for these molecules in regulating larval diapause and reactivation. A relatively conserved machinery was proposed for DA synthesis in the two ascaridoids, and endogenous Δ4- and Δ7-DAs were detected in them by LC-MS analysis. Differential transcription analysis between T. canis and A. suum suggests that ins-17 and ins-18 homologues are specifically involved in regulating development and migration in T. canis larvae in host tissues. CONCLUSION: The findings of this study provide a basis for functional explorations of insulin-like peptides, signalling hormones (i.e. DAs) and related nuclear receptors, proposed to link to development and/or parasite-host interactions in T. canis. Elucidating the functional roles of these molecules might contribute to the discovery of novel anthelmintic targets in ascaridoids.
-
ItemHigh-quality nuclear genome for Sarcoptes scabiei-A critical resource for a neglected parasite(PUBLIC LIBRARY SCIENCE, 2020-10-01)The parasitic mite Sarcoptes scabiei is an economically highly significant parasite of the skin of humans and animals worldwide. In humans, this mite causes a neglected tropical disease (NTD), called scabies. This disease results in major morbidity, disability, stigma and poverty globally and is often associated with secondary bacterial infections. Currently, anti-scabies treatments are not sufficiently effective, resistance to them is emerging and no vaccine is available. Here, we report the first high-quality genome and transcriptomic data for S. scabiei. The genome is 56.6 Mb in size, has a a repeat content of 10.6% and codes for 9,174 proteins. We explored key molecules involved in development, reproduction, host-parasite interactions, immunity and disease. The enhanced ‘omic data sets for S. scabiei represent comprehensive and critical resources for genetic, functional genomic, metabolomic, phylogenetic, ecological and/or epidemiological investigations, and will underpin the design and development of new treatments, vaccines and/or diagnostic tests.
-
ItemDafachronic acid promotes larval development in Haemonchus contortus by modulating dauer signalling and lipid metabolism(PUBLIC LIBRARY SCIENCE, 2019-07)Here, we discovered an endogenous dafachronic acid (DA) in the socioeconomically important parasitic nematode Haemonchus contortus. We demonstrate that DA promotes larval exsheathment and development in this nematode via a relatively conserved nuclear hormone receptor (DAF-12). This stimulatory effect is dose- and time-dependent, and relates to a modulation of dauer-like signalling, and glycerolipid and glycerophospholipid metabolism, likely via a negative feedback loop. Specific chemical inhibition of DAF-9 (cytochrome P450) was shown to significantly reduce the amount of endogenous DA in H. contortus; compromise both larval exsheathment and development in vitro; and modulate lipid metabolism. Taken together, this evidence shows that DA plays a key functional role in the developmental transition from the free-living to the parasitic stage of H. contortus by modulating the dauer-like signalling pathway and lipid metabolism. Understanding the intricacies of the DA-DAF-12 system and associated networks in H. contortus and related parasitic nematodes could pave the way to new, nematode-specific treatments.
-
ItemDauer signalling pathway model for Haemonchus contortus(BMC, 2019-04-29)BACKGROUND: Signalling pathways have been extensively investigated in the free-living nematode Caenorhabditis elegans, but very little is known about these pathways in parasitic nematodes. Here, we constructed a model for the dauer-associated signalling pathways in an economically highly significant parasitic worm, Haemonchus contortus. METHODS: Guided by data and information available for C. elegans, we used extensive genomic and transcriptomic datasets to infer gene homologues in the dauer-associated pathways, explore developmental transcriptomic, proteomic and phosphoproteomic profiles in H. contortus and study selected molecular structures. RESULTS: The canonical cyclic guanosine monophosphate (cGMP), transforming growth factor-β (TGF-β), insulin-like growth factor 1 (IGF-1) and steroid hormone signalling pathways of H. contortus were inferred to represent a total of 61 gene homologues. Compared with C. elegans, H. contortus has a reduced set of genes encoding insulin-like peptides, implying evolutionary and biological divergences between the parasitic and free-living nematodes. Similar transcription profiles were found for all gene homologues between the infective stage of H. contortus and dauer stage of C. elegans. High transcriptional levels for genes encoding G protein-coupled receptors (GPCRs), TGF-β, insulin-like ligands (e.g. ins-1, ins-17 and ins-18) and transcriptional factors (e.g. daf-16) in the infective L3 stage of H. contortus were suggestive of critical functional roles in this stage. Conspicuous protein expression patterns and extensive phosphorylation of some components of these pathways suggested marked post-translational modifications also in the L3 stage. The high structural similarity in the DAF-12 ligand binding domain among nematodes indicated functional conservation in steroid (i.e. dafachronic acid) signalling linked to worm development. CONCLUSIONS: Taken together, this pathway model provides a basis to explore hypotheses regarding biological processes and regulatory mechanisms (via particular microRNAs, phosphorylation events and/or lipids) associated with the development of H. contortus and related nematodes as well as parasite-host cross talk, which could aid the discovery of new therapeutic targets.