Veterinary Biosciences - Research Publications
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ItemGlobal prevalence of Ascaris infection in humans (2010-2021): a systematic review and meta-analysis.(Springer Science and Business Media LLC, 2022-11-18)BACKGROUND: Ascariasis is one of the most important neglected tropical diseases of humans worldwide. The epidemiology of Ascaris infection appears to have changed with improvements in sanitation and mass drug administration, but there is no recent information on prevalence worldwide. Here, we performed a systematic review and meta-analysis to assess the global prevalence of human Ascaris infection from 2010 to 2021. METHODS: We searched MEDLINE/PubMed, and Scopus databases for studies measuring prevalence of Ascaris infection, published between 1 January 2010 and 1 January 2022. We included studies of the general human population in endemic regions, which used accepted coprodiagnostic methods, and excluded studies of people with occupations with an increased risk or probability of ascariasis and/or specific diseases other than ascariasis. We applied random-effects models to obtain pooled prevalence estimates for six sustainable development goal regions of the world. We extrapolated the prevalence estimates to the global population in 2020, to estimate the number of individuals with Ascaris infection. We conducted multiple subgroup and meta-regression analyses to explore possible sources of heterogeneity, and to assess relationships between prevalence estimates and demographic, socio-economic, geo-climatic factors. RESULTS: Of 11,245 studies screened, we analysed 758 prevalence estimates for a total number of 4,923,876 participants in 616 studies from 81 countries. The global prevalence estimated was 11.01% (95% confidence interval: 10.27-11.78%), with regional prevalences ranging from 28.77% (7.07-57.66%) in Melanesia (Oceania) to 1.39% (1.07-1.74%) in Eastern Asia. We estimated that ~ 732 (682-782) million people harboured Ascaris worldwide in 2021. The infected people in Latin America and the Caribbean region had a higher prevalence of high intensity infection (8.4%, 3.9-14.1%). Prevalence estimates were higher in children, and people in rural communities or in countries or regions with lower income and human development indices. There was a trend for a higher prevalence in regions with increasing mean annual relative humidity, precipitation and environmental temperature. CONCLUSIONS: Our findings indicate that, despite a renewed commitment by some communities or authorities to control ascariasis, a substantial portion of the world's human population (> 0.7 billion) is infected with Ascaris. Despite the clinical and socioeconomic importance of ascariasis, many past routine surveys did not assess the intensity of Ascaris infection in people. We propose that the present findings might stimulate the development of customised strategies for the improved control and prevention of Ascaris infection worldwide.
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ItemH11-induced immunoprotection is predominantly linked to N-glycan moieties during Haemonchus contortus infection.(Frontiers Media SA, 2022)Nematodes are one of the largest groups of animals on the planet. Many of them are major pathogens of humans, animals and plants, and cause destructive diseases and socioeconomic losses worldwide. Despite their adverse impacts on human health and agriculture, nematodes can be challenging to control, because anthelmintic treatments do not prevent re-infection, and excessive treatment has led to widespread drug resistance in nematode populations. Indeed, many nematode species of livestock animals have become resistant to almost all classes of anthelmintics used. Most efforts to develop commercial anti-nematode vaccines (native or recombinant) for use in animals and humans have not succeeded, although one effective (dead) vaccine (Barbervax) has been developed to protect animals against one of the most pathogenic parasites of livestock animals - Haemonchus contortus (the barber's pole worm). This vaccine contains native molecules, called H11 and H-Gal-GP, derived from the intestine of this blood-feeding worm. In its native form, H11 alone consistently induces high levels (75-95%) of immunoprotection in animals against disease (haemonchosis), but recombinant forms thereof do not. Here, to test the hypothesis that post-translational modification (glycosylation) of H11 plays a crucial role in achieving such high immunoprotection, we explored the N-glycoproteome and N-glycome of H11 using the high-resolution mass spectrometry and assessed the roles of N-glycosylation in protective immunity against H. contortus. Our results showed conclusively that N-glycan moieties on H11 are the dominant immunogens, which induce high IgG serum antibody levels in immunised animals, and that anti-H11 IgG antibodies can confer specific, passive immunity in naïve animals. This work provides the first detailed account of the relevance and role of protein glycosylation in protective immunity against a parasitic nematode, with important implications for the design of vaccines against metazoan parasites.
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ItemThe redlegged earth mite draft genome provides new insights into pesticide resistance evolution and demography in its invasive Australian range(WILEY, 2022-12-27)Genomic data provide valuable insights into pest management issues such as resistance evolution, historical patterns of pest invasions and ongoing population dynamics. We assembled the first reference genome for the redlegged earth mite, Halotydeus destructor (Tucker, 1925), to investigate adaptation to pesticide pressures and demography in its invasive Australian range using whole-genome pool-seq data from regionally distributed populations. Our reference genome comprises 132 autosomal contigs, with a total length of 48.90 Mb. We observed a large complex of ace genes, which has presumably evolved from a long history of organophosphate selection in H. destructor and may contribute towards organophosphate resistance through copy number variation, target-site mutations and structural variants. In the putative ancestral H. destructor ace gene, we identified three target-site mutations (G119S, A201S and F331Y) segregating in organophosphate-resistant populations. Additionally, we identified two new para sodium channel gene mutations (L925I and F1020Y) that may contribute to pyrethroid resistance. Regional structuring observed in population genomic analyses indicates that gene flow in H. destructor does not homogenize populations across large geographic distances. However, our demographic analyses were equivocal on the magnitude of gene flow; the short invasion history of H. destructor makes it difficult to distinguish scenarios of complete isolation vs. ongoing migration. Nonetheless, we identified clear signatures of reduced genetic diversity and smaller inferred effective population sizes in eastern vs. western populations, which is consistent with the stepping-stone invasion pathway of this pest in Australia. These new insights will inform development of diagnostic genetic markers of resistance, further investigation into the multifaceted organophosphate resistance mechanism and predictive modelling of resistance evolution and spread.
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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, 2022-12-01)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.
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ItemNo Preview AvailableGenome-wide exploration reveals distinctive northern and southern variants of Clonorchis sinensis in the Far East(WILEY, 2023-05)Clonorchis sinensis is a carcinogenic liver fluke that causes clonorchiasis-a neglected tropical disease (NTD) affecting ~35 million people worldwide. No vaccine is available, and chemotherapy relies on one anthelmintic, praziquantel. This parasite has a complex life history and is known to infect a range of species of intermediate (freshwater snails and fish) and definitive (piscivorous) hosts. Despite this biological complexity and the impact of this biocarcinogenic pathogen, there has been no previous study of molecular variation in this parasite on a genome-wide scale. Here, we conducted the first extensive nuclear genomic exploration of C. sinensis individuals (n = 152) representing five distinct populations from mainland China, and one from Far East Russia, and revealed marked genetic variation within this species between "northern" and "southern" geographical regions. The discovery of this variation indicates the existence of biologically distinct variants within C. sinensis, which may have distinct epidemiology, pathogenicity and/or chemotherapic responsiveness. The detection of high heterozygosity within C. sinensis specimens suggests that this parasite has developed mechanisms to readily adapt to changing environments and/or host species during its life history/evolution. From an applied perspective, the identification of invariable genes could assist in finding new intervention targets in this parasite, given the major clinical relevance of clonorchiasis. From a technical perspective, the genomic-informatic workflow established herein will be readily applicable to a wide range of other parasites that cause NTDs.
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ItemNo Preview AvailableIdentification of Anthelmintic Bishomoscalarane Sesterterpenes from the Australian Marine Sponge Phyllospongia bergquistae and Structure Revision of Phyllolactones A-D(AMER CHEMICAL SOC, 2022-06-21)High-throughput screening of the NatureBank marine extract library (7616 samples) identified an extract derived from the Australian marine sponge Phyllospongia bergquistae with activity against Hemonchus contortus (barber's pole worm), an economically important parasitic nematode. Bioassay-guided fractionation of the CH2Cl2/MeOH extract from P. bergquistae led to the purification of four known bishomoscalarane sesterterpenes, phyllolactones A-D (1-4). The absolute configurations of phyllolactones B (2) and C (3) were determined by single-crystal X-ray diffraction analysis; literature and data analyses revealed the need for these chemical structures to be revised. Compounds 2-4 induced a lethal, skinny (Ski) phenotype in larvae of H. contortus at concentrations between 5.3 and 10.1 μM. These data indicate that the bishomoscalarane sesterterpene structure class warrants further investigation for nematocidal or nematostatic activity.
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ItemNo Preview AvailableUbiquitination pathway model for the barber's pole worm - Haemonchus contortus(ELSEVIER SCI LTD, 2022-08-01)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.
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ItemNo Preview AvailableAn informatic workflow for the enhanced annotation of excretory/secretory proteins of Haemonchus contortus.(Elsevier BV, 2023)Major advances in genomic and associated technologies have demanded reliable bioinformatic tools and workflows for the annotation of genes and their products via comparative analyses using well-curated reference data sets, accessible in public repositories. However, the accurate in silico annotation of molecules (proteins) encoded in organisms (e.g., multicellular parasites) which are evolutionarily distant from those for which these extensive reference data sets are available, including invertebrate model organisms (e.g., Caenorhabditis elegans - free-living nematode, and Drosophila melanogaster - the vinegar fly) and vertebrate species (e.g., Homo sapiens and Mus musculus), remains a major challenge. Here, we constructed an informatic workflow for the enhanced annotation of biologically-important, excretory/secretory (ES) proteins ("secretome") encoded in the genome of a parasitic roundworm, called Haemonchus contortus (commonly known as the barber's pole worm). We critically evaluated the performance of five distinct methods, refined some of them, and then combined the use of all five methods to comprehensively annotate ES proteins, according to gene ontology, biological pathways and/or metabolic (enzymatic) processes. Then, using optimised parameter settings, we applied this workflow to comprehensively annotate 2591 of all 3353 proteins (77.3%) in the secretome of H. contortus. This result is a substantial improvement (10-25%) over previous annotations using individual, "off-the-shelf" algorithms and default settings, indicating the ready applicability of the present, refined workflow to gene/protein sequence data sets from a wide range of organisms in the Tree-of-Life.
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ItemUsing UHPLC-MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library(BEILSTEIN-INSTITUT, 2022-11-15)In order to further expand the NatureBank open access compound library, chemical investigations of the Australian marine sponge, Ianthella basta, were undertaken since UHPLC-MS analysis of the extract from this sponge indicated the presence of a new alkaloid. Large-scale extraction and mass-directed isolation studies on the CH2Cl2/MeOH I. basta extract resulted in the purification of a new bromotyrosine-derived alkaloid, 5-debromopurealidin H (1), along with the known marine natural product, ianthesine E (2). The chemical structure of the new compound was determined following detailed spectroscopic and spectrometric data analysis. These two compounds (1 and 2) along with seven previously reported marine bromotyrosine alkaloids from the NatureBank open access library, which included psammaplysins F (3) and H (4), bastadins 4 (5), 8 (6) and 13 (7), aerothionin (8) and hexadellin A (9), were evaluated for their nematocidal activity against exsheathed third-stage larvae of Haemonchus contortus, a highly pathogenic parasite of ruminants. Of the nine compounds, bastadin 8 (6), hexadellin A (9) and bastadin 4 (5) showed inhibition towards larval motility after 72 h of exposure with IC50 values of 1.6 µM, 10.0 µM and 33.3 µM, respectively.
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ItemThe non-glycosylated protein of Toxocara canis MUC-1 interacts with proteins of murine macrophages(PUBLIC LIBRARY SCIENCE, 2022-09)Toxocariasis is a neglected parasitic disease caused predominantly by larvae of Toxocara canis. While this zoonotic disease is of major importance in humans and canids, it can also affect a range of other mammalian hosts. It is known that mucins secreted by larvae play key roles in immune recognition and evasion, but very little is understood about the molecular interactions between host cells and T. canis. Here, using an integrative approach (affinity pull-down, mass spectrometry, co-immunoprecipitation and bioinformatics), we identified 219 proteins expressed by a murine macrophage cell line (RAW264.7) that interact with prokaryotically-expressed recombinant protein (rTc-MUC-1) representing the mucin Tc-MUC-1 present in the surface coat of infective larvae of T. canis. Protein-protein interactions between rTc-MUC-1 and an actin binding protein CFL1 as well as the fatty acid binding protein FABP5 of RAW264.7 macrophages were also demonstrated in a human embryonic kidney cell line (HEK 293T). By combing predicted structural information on the protein-protein interaction and functional knowledge of the related protein association networks, we inferred roles for Tc-MUC-1 protein in the regulation of actin cytoskeletal remodelling, and the migration and phagosome formation of macrophage cells. These molecular interactions now require verification in vivo. The experimental approach taken here should be readily applicable to comparative studies of other ascaridoid nematodes (e.g. T. cati, Anisakis simplex, Ascaris suum and Baylisascaris procyonis) whose larvae undergo tissue migration in accidental hosts, including humans.