Extending from PARs in Caenorhabditis elegans to homologues in Haemonchus contortus and other parasitic nematodes

Parasitology ◽  
2006 ◽  
Vol 134 (4) ◽  
pp. 461-482 ◽  
Author(s):  
S. NIKOLAOU ◽  
R. B. GASSER
Keyword(s):  
Caenorhabditis Elegans ◽  
Haemonchus Contortus ◽  
Asymmetric Cell Division ◽  
Small Ruminants ◽  
Future Research ◽  
Parasitic Nematodes ◽  
Par Proteins ◽  
Surface Receptors ◽  
Cytoskeletal Dynamics ◽  
Free Living Nematode

Signal transduction molecules play key roles in the regulation of developmental processes, such as morphogenesis, organogenesis and cell differentiation in all organisms. They are organized into ‘pathways’ that represent a coordinated network of cell-surface receptors and intracellular molecules, being involved in sensing environmental stimuli and transducing signals to regulate or modulate cellular processes, such as gene expression and cytoskeletal dynamics. A particularly important group of molecules implicated in the regulation of the cytoskeleton for the establishment and maintenance of cell polarity is the PAR proteins (derived from partition defective in asymmetric cell division). The present article reviews salient aspects of PAR proteins involved in the early embryonic development and morphogenesis of the free-living nematode Caenorhabditis elegans and some other organisms, with an emphasis on the molecule PAR-1. Recent advances in the knowledge and understanding of PAR-1 homologues from the economically important parasitic nematode, Haemonchus contortus, of small ruminants is summarized and discussed in the context of exploring avenues for future research in this area for parasitic nematodes.

scholarly journals Binding of Hematin by a New Class of Glutathione Transferase from the Blood-Feeding Parasitic Nematode Haemonchus contortus

2004 ◽  
Vol 72 (5) ◽  
pp. 2780-2790 ◽  
Author(s):  
Arjan J. van Rossum ◽  
James R. Jefferies ◽  
Frans A. M. Rijsewijk ◽  
E. James LaCourse ◽  
Paul Teesdale-Spittle ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Parasitic Nematode ◽  
Glutathione Transferase ◽  
Small Ruminants ◽  
Blood Feeding ◽  
Mammalian Host ◽  
Affinity Binding ◽  
High Affinity Binding ◽  
High Affinity ◽  
Free Living Nematode

ABSTRACT The phase II detoxification system glutathione transferase (GST) is associated with the establishment of parasitic nematode infections within the gastrointestinal environment of the mammalian host. We report the functional analysis of a GST from an important worldwide parasitic nematode of small ruminants, Haemonchus contortus. This GST shows limited activity with a range of classical GST substrates but effectively binds hematin. The high-affinity binding site for hematin was not present in the GST showing the most identity, CE07055 from the free-living nematode Caenorhabditis elegans. This finding suggests that the high-affinity binding of hematin may represent a parasite adaptation to blood or tissue feeding from the host.

The use of Caenorhabditis elegans in parasitic nematode research

Parasitology ◽  
2004 ◽  
Vol 128 (S1) ◽  
pp. S49-S70 ◽  
Author(s):  
J. S. GILLEARD
Keyword(s):  
Caenorhabditis Elegans ◽  
Parasitic Nematode ◽  
Expression System ◽  
Nematode Species ◽  
Current Status ◽  
Evolutionary Development ◽  
Parasitic Nematodes ◽  
Free Living ◽  
C Elegans ◽  
Free Living Nematode

There is increasing interest in the use of the free-living nematode Caenorhabditis elegans as a tool for parasitic nematode research and there are now a number of compelling examples of its successful application. C. elegans has the potential to become a standard tool for molecular helminthology researchers, just as yeast is routinely used by molecular biologists to study vertebrate biology. However, in order to exploit C. elegans in a meaningful manner, we need a detailed understanding of the extent to which different aspects of C. elegans biology have been conserved with particular groups of parasitic nematodes. This review first considers the current state of knowledge regarding the conservation of genome organisation across the nematode phylum and then discusses some recent evolutionary development studies in free-living nematodes. The aim is to provide some important concepts that are relevant to the extrapolation of information from C. elegans to parasitic nematodes and also to the interpretation of experiments that use C. elegans as a surrogate expression system. In general, examples have been specifically chosen because they highlight the importance of careful experimentation and interpretation of data. Consequently, the focus is on the differences that have been found between nematode species rather than the similarities. Finally, there is a detailed discussion of the current status of C. elegans as a heterologous expression system to study parasite gene function and regulation using successful examples from the literature.

scholarly journals Characterization of a Rhodanese Homologue from Haemonchus Contortus and its Immune-Modulatory Effects on Goat Immune Cells in Vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Parasitic Nematodes ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background: Suppression and modulation of the immune response of the host by nematode parasites have been reported widely. Rhodaneses or thiosulfate: cyanide sulfurtransferases are present in a wide range of organisms, such as archea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homology could bind by goat peripheral blood mononuclear cells (PBMCs) in vivo.Results: In the present study, we cloned and produced recombinant rhodanese protein originated from Haemonchus contortus (rHCRD), which was one of the parasitic nematodes of small ruminants. The effect of this protein on modulating the immunity of goat PBMC and monocyte was studied in the current work. The predominant localization of the natural HCRD protein was verified as the bowel wall and body surface of worms, according to the immunohistochemical tests. It was proved in this study that the serum produced by artificially infecting goats with H. contortus successfully recognized rHCRD which conjugated goat PBMCs. The rHCRD was co-incubated with goat PBMCs to observe the immunomodulatory effect on proliferation, apoptosis and secretion of cytokines exerted by HCRD. The results showed that the interaction of rHCRD suppressed proliferation of goat PBMCs stimulated by ConA but did not induce the apoptosis of goat PBMCs. After rHCRD exposure, the production of TNF-α and IFN-γ were significantly decreased, however, it significantly increased the secretion of IL-10 and TGF-β1 in goat PBMCs. Phagocytotic assay by FITC-dextran internalization showed that rHCRD inhibited the phagocytosis of goat monocytes. Moreover, rHCRD could down-regulate the expression of MHC-II on goat monocytes in a dose-dependent manner. Conclusions: These discoveries proposed a possible target as immunomodulator, which was potentially beneficial to illuminate the interaction between parasites and hosts in the molecular level and hunt for innovative protein species as candidate targets of drug and vaccine.

scholarly journals Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans

2013 ◽  
Vol 44 (1) ◽  
pp. 111 ◽  
Author(s):  
Brett Roberts ◽  
Aristotelis Antonopoulos ◽  
Stuart M Haslam ◽  
Alison J Dicker ◽  
Tom N McNeilly ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Haemonchus Contortus ◽  
Vaccine Candidate ◽  
Nematode Caenorhabditis Elegans ◽  
Free Living ◽  
Free Living Nematode

scholarly journals A Zinc Metalloprotease nas-33 Is Required for Molting and Survival in Parasitic Nematode Haemonchus contortus

2021 ◽  
Vol 9 ◽  
Author(s):  
Yan Huang ◽  
Jie Wu ◽  
Xueqiu Chen ◽  
Danni Tong ◽  
Jingru Zhou ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Parasitic Nematode ◽  
Large Family ◽  
Parasitic Nematodes ◽  
Larval Stages ◽  
Zinc Metalloprotease ◽  
Molting Process ◽  
Survival And Development ◽  
Free Living Nematode

Molting is of great importance for the survival and development of nematodes. Nematode astacins (NAS), a large family of zinc metalloproteases, have been proposed as novel anthelmintic targets due to their multiple roles in biological processes of parasitic nematodes. In this study, we report a well conserved nas-33 gene in nematodes of clade V and elucidate how this gene is involved in the molting process of the free-living nematode Caenorhabditis elegans and the parasitic nematode Haemonchus contortus. A predominant transcription of nas-33 is detected in the larval stages of these worms, particularly in the molting process. Knockdown of this gene results in marked molecular changes of genes involved in cuticle synthesis and ecdysis, compromised shedding of the old cuticle, and reduced worm viability in H. contortus. The crucial role of nas-33 in molting is closely associated with a G protein beta subunit (GPB-1). Suppression of both nas-33 and gpb-1 blocks shedding of the old cuticle, compromises the connection between the cuticle and hypodermis, and leads to an increased number of sick and dead worms, indicating essentiality of this module in nematode development and survival. These findings reveal the functional role of nas-33 in nematode molting process and identify astacins as novel anthelmintic targets for parasitic nematodes of socioeconomic significance.

scholarly journals Nanoparticles as Alternatives for the Control of Haemonchus contortus: A Systematic Approach to Unveil New Anti-haemonchiasis Agents

2021 ◽  
Vol 8 ◽  
Author(s):  
Rehman Ali ◽  
Nisar Ahmad ◽  
Sakina Mussarat ◽  
Abdul Majid ◽  
Sultan F. Alnomasy ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Anthelmintic Resistance ◽  
Small Ruminants ◽  
Gastrointestinal Nematode ◽  
Future Research ◽  
Cymbopogon Citratus ◽  
Toxicological Effects ◽  
Nano Emulsion

Haemonchus contortus is an infectious gastrointestinal nematode parasite of small ruminants. This study addresses the in vitro/in vivo anti-haemonchiasis potential, toxicological effects, and mechanism of action of nanoparticles. Online databases were used to search and retrieve the published literature (2000 to 2021). A total of 18 articles were selected and reviewed, out of which, 13 (72.2%) studies reported in vitro, 9 (50.0%) in vivo, and 4 (22.2%) both in vitro/in vivo efficacy of different nanoparticles. Mostly, organic nanoparticles (77.7%) were used including polymeric (85.7%) and lipid nanoparticles (14.3%). The highest efficacy, in vitro, of 100% resulted from using encapsulated bromelain against eggs, larvae, and adult worm mortality at 4, 2, and 1 mg/ml, respectively. While in vivo, encapsulated Eucalyptus staigeriana oil reduced worm burden by 83.75% and encapsulated Cymbopogon citratus nano-emulsion by 83.1%. Encapsulated bromelain, encapsulated Eucalyptus staigeriana oil, and encapsulated Cymbopogon citratus nano-emulsion were safe and non-toxic in vivo. Encapsulated bromelain damaged the cuticle, caused paralysis, and death. Nanoparticles could be a potential source for developing novel anthelmintic drugs to overcome the emerging issue of anthelmintic resistance in H. contortus. Studies on molecular effects, toxicological consequences, and different pharmacological targets of nanoparticles are required in future research.

scholarly journals Caenorhabditis elegans: nature and nurture gift to nematode parasitologists

Parasitology ◽  
2017 ◽  
Vol 145 (8) ◽  
pp. 979-987 ◽  
Author(s):  
Gustavo Salinas ◽  
Gastón Risi
Keyword(s):  
Animal Model ◽  
Caenorhabditis Elegans ◽  
Parasitic Nematode ◽  
Model Organism ◽  
Parasitic Nematodes ◽  
Free Living ◽  
C Elegans ◽  
Free Living Nematode ◽  
Basic Biology ◽  
Nature And Nurture

AbstractThe free-living nematode Caenorhabditis elegans is the simplest animal model organism to work with. Substantial knowledge and tools have accumulated over 50 years of C. elegans research. The use of C. elegans relating to parasitic nematodes from a basic biology standpoint or an applied perspective has increased in recent years. The wealth of information gained on the model organism, the use of the powerful approaches and technologies that have advanced C. elegans research to parasitic nematodes and the enormous success of the omics fields have contributed to bridge the divide between C. elegans and parasite nematode researchers. We review key fields, such as genomics, drug discovery and genetics, where C. elegans and nematode parasite research have convened. We advocate the use of C. elegans as a model to study helminth metabolism, a neglected area ready to advance. How emerging technologies being used in C. elegans can pave the way for parasitic nematode research is discussed.

Characterization of heat shock protein 70 gene fromHaemonchus contortusand its expression and promoter analysis inCaenorhabditis elegans

Parasitology ◽  
2013 ◽  
Vol 140 (6) ◽  
pp. 683-694 ◽  
Author(s):  
HONGLI ZHANG ◽  
QIANJIN ZHOU ◽  
YI YANG ◽  
XUEQIU CHEN ◽  
BAOLONG YAN ◽  
...  
Keyword(s):  
Heat Shock ◽  
Haemonchus Contortus ◽  
Expression Patterns ◽  
Small Ruminants ◽  
Green Fluorescence Protein ◽  
Bioinformatic Analysis ◽  
Parasitic Nematodes ◽  
Hsp70 Mrna ◽  
C Elegans ◽  
Larval Stages

SUMMARYHaemonchus contortusinfections in small ruminants are of major economic importance worldwide. Heat shock proteins (HSPs) are a family of molecular chaperones that play important roles in the process of invasion and survival of nematodes. Although HSP70 has been identified in several parasitic nematodes, little is known of its distribution and function inHaemonchus contortus. The aims of this study were to characterize HSP70 fromHaemonchus contortus(designed as Hc-hsp70), express Hc-hsp70 and analyse the promoter activity inCaenorhabditis elegans. Bioinformatic analysis revealed that the open reading frame of the Hc-hsp70 cDNA encodes a 646-amino acid peptide, which is highly conserved in comparison to HSP70 in other nematodes. Phylogenetic analysis indicated thatH. contortusis closely related toCaenorhabditis. The 5′-flanking region promoted green fluorescence protein (GFP) expression in the intestine in all larval stages and adult with 2 expression patterns inC. elegans. Expression of Hc-hsp70 mRNA transcripts inC. elegansincreased following 2, 4, 6 h of heat shock and peaked at 4 h. However, its expression induced down-regulation ofhsp-1ofC. elegans. These results suggest that theH. contortushsp70 might have a similar function to that ofC. elegans hsp-1.

scholarly journals A Transcription Factor DAF5 Functions in Haemonchus Contortus Development

2021 ◽  
Author(s):  
Wenda Di ◽  
Fangfang Li ◽  
Li He ◽  
Chunqun Wang ◽  
Caixian Zhou ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Developmental Stages ◽  
Reproductive Organs ◽  
Bimolecular Fluorescence Complementation ◽  
Parasitic Nematodes ◽  
C Elegans ◽  
Free Living Nematode ◽  
And Function ◽  
Reproductive Processes

Abstract Background: Daf5 (Dauer abnormal formation gene), located in the downstream of DAF-7 signalling pathway, mainly functions in dauer formation and reproductive processes in the free-living nematode Caenorhabditis elegans. Although its structure and function have been studied clearly in C. elegans, it was totally unknown in Haemonchus contortus, a socio-economically important parasitic nematode of gastric ruminants.Methods: Here, we identified and characterized a homologue of Daf5, Hcdaf5 and its inferred product (HcDAF5) in H. contortus. Using an integrated molecular approach, we studied the transcriptional profiles of Hcdaf5 and the anatomical expression of HcDAF5 in H. contortus. RNA interference (RNAi) was performed to explore its function in transition from the exsheathed third-stage larvae (xL3) to the fourth-stage larvae (L4) in vitro. Interaction of HcDAF5 and HcDAF3 (a co-SMAD) was also detected by bimolecular fluorescence complementation system (BiFc) in vitro.Results: Here, we showed that HcDAF5 is a member of the Sno/Ski superfamily. Hcdaf5 was transcribed in all developmental stages of H. contortus, with a significant up-regulation in L3. Immunohistochemistry localized native HcDAF5 to the reproductive organs, cuticle and intestine. RNAi revealed specific siRNAs (small interfering RNA) could retard the xL3 development. In addition, the interaction between HcDAF5 and HcDAF3 indicated the SDS box region of HcDAF5 is dispensable for the binding of HcDAF5 to HcDAF3 and the region in HcDAF3 that binds to HcDAF5 is MH2 domain.Conclusion: In summary, these findings show that Hcdaf5 functions in developmental processes of H. contortus, and this is the first characterization of daf-5 gene in parasitic nematodes.

scholarly journals Two novel loci underlie natural differences in Caenorhabditis elegans macrocyclic lactone responses

2021 ◽  
Author(s):  
Kathryn S. Evans ◽  
Janneke Wit ◽  
Lewis Stevens ◽  
Steffen R. Hahnel ◽  
Briana Rodriguez ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Haemonchus Contortus ◽  
Macrocyclic Lactone ◽  
Parasitic Nematode ◽  
Anthelmintic Resistance ◽  
Recombinant Inbred Lines ◽  
Parasitic Nematodes ◽  
C Elegans ◽  
The Future ◽  
Genomic Regions

AbstractParasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C. elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C. elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C. elegans as a model to better understand ML resistance in parasitic nematodes.Author SummaryParasitic nematodes infect plants, animals, and humans, causing major health and economic burdens worldwide. Parasitic nematode infections are generally treated efficiently with a class of drugs named anthelmintics. However, resistance to many of these anthelmintic drugs, including macrocyclic lactones (MLs), is rampant and increasing. Therefore, it is essential that we understand how these drugs act against parasitic nematodes and, conversely, how nematodes gain resistance in order to better treat these infections in the future. Here, we used the non-parasitic nematode Caenorhabditis elegans as a model organism to study ML resistance. We leveraged natural genetic variation between strains of C. elegans with differential responses to abamectin to identify three genomic regions on chromosome V, each containing one or more genes that contribute to ML resistance. Two of these loci have not been previously discovered and likely represent novel resistance mechanisms. We also compared the genes in these two novel loci to the genes found within genomic regions linked to ML resistance in the parasite Haemonchus contortus and found several cases of overlap between the two species. Overall, this study highlights the advantages of using C. elegans to understand anthelmintic resistance in parasitic nematodes.

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