scholarly journals Complementary Approaches to Understand Anthelmintic Resistance Using Free-Living and Parasitic Nematodes

2020 ◽  
Author(s):  
Janneke Wit ◽  
Clayton Dilks ◽  
Erik Andersen
Keyword(s):  
Haemonchus Contortus ◽  
Parasitic Nematode ◽  
Anthelmintic Resistance ◽  
Nematode Species ◽  
The Other ◽  
Parasitic Nematodes ◽  
Mechanisms Of Resistance ◽  
Free Living ◽  
Sustained Efficacy ◽  
Modes Of Action

Anthelmintic drugs are the major line of defense against parasitic nematode infections, but the arsenal is limited and resistance threatens sustained efficacy of the available drugs. Discoveries of the modes of action of these drugs and mechanisms of resistance have predominantly come from studies of a related non-parasitic nematode species, Caenorhabditis elegans, and the parasitic nematode Haemonchus contortus. Here, we discuss how our understanding of anthelmintic resistance and modes of action came from the interplay of results from each of these species. We argue that this “cycle of discovery”, where results from one species inform the design of experiments in the other, can use the complementary strengths of both to understand anthelmintic modes of action and mechanisms of resistance.

Complementary Approaches to Understand Anthelmintic Resistance Using Free-Living and Parasitic Nematodes

2020 ◽  
Author(s):  
Janneke Wit ◽  
Clayton Dilks ◽  
Erik Andersen
Keyword(s):  
Haemonchus Contortus ◽  
Parasitic Nematode ◽  
Anthelmintic Resistance ◽  
Animal Health ◽  
Nematode Species ◽  
Parasitic Nematodes ◽  
Mechanisms Of Resistance ◽  
Free Living ◽  
Powerful Approach ◽  
Anthelmintic Drugs

Parasitic nematode infections impact human and animal health globally, especially in the developing world. Anthelmintic drugs are the major line of defense against these infections, but the arsenal is limited. Additionally, anthelmintic resistance is widespread in veterinary parasites and an emerging threat in human parasites. Discoveries of the mode of action of these drugs and mechanisms of resistance have predominantly come from studies of a related non-parasitic nematode species, Caenorhabditis elegans, and the parasitic nematode Haemonchus contortus. Here, we discuss recent progress understanding anthelmintic resistance using these two species and how that progress relates to laboratory and field-based studies of veterinary helminths. We present a powerful approach enabled by the strengths of both nematode species to understand mechanisms of resistance and modes of action of anthelmintic drugs.

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 Diversity of plant parasitic nematodes associated with rhizosphere of maize from different areas of district Rajouri, Jammu and Kashmir, India

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Kaisar Ahmad Allie ◽  
Ali Asghar Shah ◽  
Shaheen Majeed Wani ◽  
Kaisar Ahmad Bhat ◽  
Nazia Kouser ◽  
...  
Keyword(s):  
Parasitic Nematode ◽  
Nematode Species ◽  
The Other ◽  
Parasitic Nematodes ◽  
Plant Parasitic Nematodes ◽  
Absolute Frequency ◽  
Jammu And Kashmir ◽  
Maize Plants ◽  
Pratylenchus Zeae ◽  
Plant Parasitic

Diversity of plant parasitic nematodes in the rhizosphere of maize (Zea mays) from some areas of District Rajouri, Jammu and Kashmir was studied. A total of ten plant parasitic nematode species were found to be associated with the rhizosphere of maize plants in these areas. The nematode species were Pratylenchus zeae, P. brachyurus, Helicotylenchus dihystera, Longidorus brevicaudatus, L. elongatus, Xiphinema diversicadatum, X. elongatum, Tylenchorhynchus spp. Ditylenchus spp. and Criconemoides spp. The most dominant and frequently occurring species was found to be P. zeae, with absolute frequency of 86.66% followed by P. brachyurus (80%), H. dihystera, (76.66%) and L. brevicaudatus (73.33). Contrarily, the least frequent was Criconemoides spp. (36.66%) followed by Tylenchorhynchus spp. and Ditylenchus spp. with absolute frequencies of 53.33% and 60%. Similar trend was observed in case of relative frequencies. In case of P. zeae, mean density of 56 and relative density of 16.05% was observed followed by P. brachyurus and H. dihystera with mean densities and relative densities of 50.33, 14.43% and 49, 14.04% respectively. On the other hand, Criconemoides spp. and Tylenchorhynchus spp. showed mean densities of 6.33 and 23.33 and absolute densities of 1.81% and 6.68% respectively. P. zeae exhibited high prominence value of 57.85 followed by P. brachyurus (49.96). The least prominence value was found in Criconemoides spp. (4.05) followed by Tylenchorhynchus spp. with prominence value of 18.30.

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.

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

2021 ◽  
Vol 17 (3) ◽  
pp. e1009297
Author(s):  
Kathryn S. Evans ◽  
Janneke Wit ◽  
Lewis Stevens ◽  
Steffen R. Hahnel ◽  
Briana Rodriguez ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Haemonchus Contortus ◽  
Macrocyclic Lactone ◽  
Recombinant Inbred Lines ◽  
Nematode Species ◽  
Inbred Lines ◽  
Parasitic Nematodes ◽  
Near Isogenic Lines ◽  
Free Living ◽  
Genomic Regions

Parasitic 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 for most of these drugs. 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.

scholarly journals Susceptible trichostrongyloid species mask presence of benzimidazole-resistant Haemonchus contortus in cattle

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Khalid M. Mohammedsalih ◽  
Jürgen Krücken ◽  
Ahmed Bashar ◽  
Fathel-Rahman Juma ◽  
Abdalhakaim A. H. Abdalmalaik ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Epidemiological Data ◽  
Nematode Species ◽  
Parasitic Nematodes ◽  
Molecular Approaches ◽  
Tubulin Genes ◽  
Faecal Egg Count ◽  
Third Stage ◽  
Before And After ◽  
Β Tubulin

Abstract Background Benzimidazole (BZ) anthelmintics are widely used to control infections with parasitic nematodes, but BZ resistance is an emerging threat among several nematode species infecting humans and animals. In Sudan, BZ-resistant Haemonchus contortus populations were recently reported in goats in South Darfur State. The objective of this study was to collect data regarding the situation of BZ resistance in cattle parasitic nematodes in South Darfur using phenotypic and molecular approaches, besides providing some epidemiological data on nematodes in cattle. Methods The faecal egg count reduction test and the egg hatch test (EHT) were used to evaluate benzimidazole efficacy in cattle nematodes in five South Darfur study areas: Beleil, Kass, Nyala, Rehed Al-Birdi and Tulus. Genomic DNA was extracted from pools of third-stage larvae (L3) (n = 40) during trials, before and after treatment, and pools of adult male Haemonchus spp. (n = 18) from abattoirs. The polymorphisms F167Y, E198A and F200Y in isotype 1 β-tubulin genes of H. contortus and H. placei were analysed using Sanger and pyrosequencing. Results Prevalence of gastro-intestinal helminths in cattle was 71% (313/443). Reduced albendazole faecal egg count reduction efficacy was detected in three study areas: Nyala (93.7%), Rehed Al-Birdi (89.7%) and Tulus (88.2%). In the EHT, EC50 values of these study areas ranged between 0.032 and 0.037 µg/ml thiabendazole. Genus-specific PCRs detected the genera Haemonchus, Trichostrongylus and Cooperia in L3 samples collected after albendazole treatment. Sanger sequencing followed by pyrosequencing assays did not detect elevated frequencies of known BZ resistance-associated alleles in codon F167Y, E198A and F200Y in isotype 1 β-tubulin gene of H. placei (≤ 11.38%). However, polymorphisms were detected in H. contortus and in samples with mixed infections with H. contortus and H. placei at codon 198, including E198L (16/58), E198V (2/58) and potentially E198Stop (1/58). All pooled L3 samples post-albendazole treatment (n = 13) were identified as H. contortus with an E198L substitution at codon 198. Conclusions To the knowledge of the authors, this is the first report of reduced albendazole efficacy in cattle in Sudan and is the first study describing an E198L substitution in phenotypically BZ-resistant nematodes collected from cattle.

scholarly journals Prospects of Using High-Throughput Proteomics to Underpin the Discovery of Animal Host–Nematode Interactions

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 825
Author(s):  
Tao Wang ◽  
Robin Gasser
Keyword(s):  
Mass Spectrometry ◽  
High Throughput ◽  
Anthelmintic Resistance ◽  
Nematode Species ◽  
Economic Losses ◽  
Future Research ◽  
Parasitic Nematodes ◽  
Public Health Burden ◽  
Host Parasite Interactions ◽  
Host Parasite

Parasitic nematodes impose a significant public health burden, and cause major economic losses to agriculture worldwide. Due to the widespread of anthelmintic resistance and lack of effective vaccines for most nematode species, there is an urgent need to discover novel therapeutic and vaccine targets, informed through an understanding of host–parasite interactions. Proteomics, underpinned by genomics, enables the global characterisation proteins expressed in a particular cell type, tissue and organism, and provides a key to insights at the host–parasite interface using advanced high-throughput mass spectrometry-based proteomic technologies. Here, we (i) review current mass-spectrometry-based proteomic methods, with an emphasis on a high-throughput ‘bottom-up’ approach; (ii) summarise recent progress in the proteomics of parasitic nematodes of animals, with a focus on molecules inferred to be involved in host–parasite interactions; and (iii) discuss future research directions that could enhance our knowledge and understanding of the molecular interplay between nematodes and host animals, in order to work toward new, improved methods for the treatment, diagnosis and control of nematodiases.

scholarly journals Genomic landscape of drug response reveals novel mediators of anthelmintic resistance

2021 ◽  
Author(s):  
Stephen R Doyle ◽  
Roz Laing ◽  
David Bartley ◽  
Alison Morrison ◽  
Nancy Holroyd ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Genetic Basis ◽  
Parasitic Nematode ◽  
Anthelmintic Resistance ◽  
Forward Genetics ◽  
Parasitic Nematodes ◽  
Genomic Landscape ◽  
Genetic Cross ◽  
Novel Alleles ◽  
Host Parasite

Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to tracking and combatting their spread. Here, we use a genetic cross in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies novel alleles for resistance to benzimidazoles and levamisole and implicates the transcription factor, cky-1, in ivermectin resistance. This gene is within a locus under selection in ivermectin resistant populations worldwide; functional validation using knockout and gene expression experiments supports a role for cky-1 overexpression in ivermectin resistance. Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode, and identifies variants for the development of molecular diagnostics to combat drug resistance in the field.

scholarly journals Differentiated effects of parasitic nematodes Phasmarhabditis hermaphrodita on slugs of the genus Deroceras and snails of the genus Arion

2005 ◽  
Vol 53 (4) ◽  
pp. 171-176
Author(s):  
Pavlína Šenoldová ◽  
Jiří Rotrekl
Keyword(s):  
Parasitic Nematode ◽  
Nematode Species ◽  
Field Conditions ◽  
Parasitic Nematodes ◽  
The Family ◽  
Snail Family ◽  
Phasmarhabditis Hermaphrodita ◽  
Differentiated Effects

This paper compares efficiency of preparations based on a parasitic nematode species Phasmarhabditis hermaphrodita with a molluscocide containing methiocarb as an effective substance. Parasitic nematodes by the family Agriolimacidae showed a significantly better effect on mortality and reduction of the percentage of damaged plants than the methiocarb-based preparation. Under laboratory and field conditions, the efficiency of parasitic nematodes on the family Agriolimacidae ranged from 84% to 94% and from 81% to 94%, resp., while the percentages of damaged plants were minimal in both cases. The corresponding effects of the methiocarb-based molluscocide were only 35% and 21%, resp. The effect of parasitic P. hermaphrodita nematodes on members of the snail family Arionidae was not demonstrated both under laboratory and field conditons and the mortality was up to 6% with a total defoliation of plants. Under laboratory and field conditions, the mortality of slugs from the genus Arion after the application of methiocarb-based preparation was 53% and 38%, resp. However, the damage of plants was significant and it reached nearly 67% and 60% under laboratory and field conditions, resp.

scholarly journals Comparison of two in vitro methods for the detection of ivermectin resistance in Haemonchus contortus in sheep

2016 ◽  
Vol 53 (2) ◽  
pp. 120-125 ◽  
Author(s):  
M. Urda Dolinská ◽  
A. Königová ◽  
M. Babják ◽  
M. Várady
Keyword(s):  
Drug Resistance ◽  
Haemonchus Contortus ◽  
Anthelmintic Resistance ◽  
Economic Losses ◽  
Parasitic Nematodes ◽  
Migration Inhibition ◽  
In Vitro Methods ◽  
Parasitic Helminths

SummaryGastrointestinal parasitic nematodes in sheep cause severe economic losses. Anthelmintics are the most commonly used drugs for prophylaxis and therapy against parasitic helminths. The problem of drug resistance has developed for all commercially available anthelmintics in several genera and classes of helminths. In vitro and in vivo tests are used to detect anthelmintic resistance. Two in vitro methods (larval migration inhibition test and micromotility test) for the detection of ivermectin (IVM) resistance were compared using IVM-resistant and IVM-susceptible isolates of Haemonchus contortus. The degree of resistance for each test was expressed as a resistance factor (RF). The micromotility test was more sensitive for quantitatively measuring the degree of resistance between susceptible and resistant isolates. The RFs for this test for IVM and eprinomectin ranged from 1.00 to 108.05 and from 3.87 to 32.32, respectively.

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