scholarly journals Anthelmintic resistance and homeostatic plasticity (Brugia malayi)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sudhanva S. Kashyap ◽  
Saurabh Verma ◽  
Mark McHugh ◽  
Mengisteab Wolday ◽  
Paul D. Williams ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Anthelmintic Resistance ◽  
Brugia Malayi ◽  
Cytosolic Calcium ◽  
Homeostatic Plasticity ◽  
Parasitic Nematodes ◽  
Excitable Cells ◽  
Spastic Paralysis ◽  
Invertebrate Species ◽  
Therapeutic Drugs

AbstractHomeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been explored in parasitic nematodes when treated with therapeutic drugs. Here we have studied the adaptation of Brugia malayi to exposure to the anthelmintic, levamisole that activates muscle AChR ion-channels. We found three phases of the Brugia malayi motility responses as they adapted to levamisole: an initial spastic paralysis; a flaccid paralysis that follows; and finally, a recovery of motility with loss of sensitivity to levamisole at 4 h. Motility, calcium-imaging, patch-clamp and molecular experiments showed the muscle AChRs are dynamic with mechanisms that adjust their subtype composition and sensitivity to levamisole. This homeostatic plasticity allows the parasite to adapt resisting the anthelmintic.

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 In Vitro Efficacy of Aqueous and Methanol Extract of Cassia siamea Against the Motility of Caenorhabditis elegans

2020 ◽  
Vol 31 (3) ◽  
pp. 145-159
Author(s):  
Haladu Ali Gagman ◽  
Nik Ahmad Irwan Izzauddin Nik Him ◽  
Hamdan Ahmad ◽  
Shaida Fariza Sulaiman ◽  
Rahmad Zakaria ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Methanol Extract ◽  
Anthelmintic Resistance ◽  
Gastrointestinal Nematode ◽  
Parasitic Nematodes ◽  
Cassia Siamea ◽  
Methanol Extracts ◽  
C Elegans ◽  
Significant Difference

Gastrointestinal nematode infections can cause great losses in revenue due to decrease livestock production and animal death. The use of anthelmintic to control gastrointestinal nematode put a selection pressure on nematode populations which led to emergence of anthelmintic resistance. Because of that, this study was carried out to investigate the efficacy of aqueous and methanol extract of Cassia siamea against the motility of C. elegans Bristol N2 and C. elegans DA1316. Caenorhabditis elegans Bristol N2 is a susceptible strain and C. elegans DA1316 is an ivermectin resistant strain. In vitro bioassay of various concentrations of (0.2, 0.6, 0.8, 1.0 and 2.0 mg mL–1) aqueous and methanol extracts of C. siamea was conducted against the motility of L4 larvae of C. elegans Bristol N2 and C. elegans DA1316. The L4 larvae were treated with 0.02 μg mL–1 of ivermectin served as positive control while those in M9 solution served as negative control. The activity of the extracts was observed after 24 h and 48 h. A significant difference was recorded in the extract performance compared to control at (P < 0.001) after 48 h against the motility of the larvae of both strains. The methanol extracts inhibited the motility of C. elegans Bristol N2 by 86.7% as well as DA1316 up to 84.9% at 2.0 mg mL–1 after 48 h. The methanol extract was more efficient than aqueous extract (P < 0.05) against the motility of both strains of C. elegans. Cassia siamea may be used as a natural source of lead compounds for the development of alternative anthelmintic against parasitic nematodes as well ivermectin resistant strains of nematodes.

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.

scholarly journals Anthelmintic resistance: markers for resistance, or susceptibility?

Parasitology ◽  
2010 ◽  
Vol 138 (2) ◽  
pp. 160-174 ◽  
Author(s):  
R. N. BEECH ◽  
P. SKUCE ◽  
D. J. BARTLEY ◽  
R. J. MARTIN ◽  
R. K. PRICHARD ◽  
...  
Keyword(s):  
Anthelmintic Resistance ◽  
Treatment Strategies ◽  
Detection Methods ◽  
Parasitic Nematodes ◽  
Specific Amino Acid ◽  
P Glycoprotein ◽  
Site Of Action ◽  
Macrocyclic Lactone Resistance ◽  
Specific Receptors ◽  
Resistance Markers

SUMMARYThe Consortium for Anthelmintic Resistance and Susceptibility (CARS) brings together researchers worldwide, with a focus of advancing knowledge of resistance and providing information on detection methods and treatment strategies. Advances in this field suggest mechanisms and features of resistance that are shared among different classes of anthelmintic. Benzimidazole resistance is characterized by specific amino acid substitutions in beta-tubulin. If present, these substitutions increase in frequency upon drug treatment and lead to treatment failure. In the laboratory, sequence substitutions in ion-channels can contribute to macrocyclic lactone resistance, but there is little evidence that they are significant in the field. Changes in gene expression are associated with resistance to several different classes of anthelmintic. Increased P-glycoprotein expression may prevent drug access to its site of action. Decreased expression of ion-channel subunits and the loss of specific receptors may remove the drug target. Tools for the identification and genetic analysis of parasitic nematodes and a new online database will help to coordinate research efforts in this area. Resistance may result from a loss of sensitivity as well as the appearance of resistance. A focus on the presence of anthelmintic susceptibility may be as important as the detection of resistance.

Evaluation of the Egg Hatch Assay and the Larval Migration Inhibition Assay to detect anthelmintic resistance in cattle parasitic nematodes on farms

2012 ◽  
Vol 61 (4) ◽  
pp. 614-618 ◽  
Author(s):  
Janina Demeler ◽  
Nina Kleinschmidt ◽  
Ursula Küttler ◽  
Regine Koopmann ◽  
Georg von Samson-Himmelstjerna
Keyword(s):  
Anthelmintic Resistance ◽  
Parasitic Nematodes ◽  
Inhibition Assay ◽  
Migration Inhibition ◽  
Egg Hatch ◽  
Larval Migration ◽  
Egg Hatch Assay

scholarly journals Worm-control practices and prevalence of anthelmintic resistance using in vivo FECRTs on smallholder sheep farms in Lithuania

2016 ◽  
Vol 53 (1) ◽  
pp. 24-30 ◽  
Author(s):  
T. Kupčinskas ◽  
I. Stadalienė ◽  
A. Šalomskas ◽  
P. Trusevičius ◽  
M. Varady ◽  
...  
Keyword(s):  
Anthelmintic Resistance ◽  
Gastrointestinal Nematodes ◽  
Parasitic Nematodes ◽  
Future Studies ◽  
Faecal Samples ◽  
Two Samples ◽  
Faecal Egg Count ◽  
Worm Control

SummaryThis study determined the prevalence of anthelmintic resistance (AR) in parasitic nematodes on smallholder sheep farms in Lithuania from April to November 2014. Faecal samples were collected from two groups of 10-15 sheep treated with fenbendazole (FBZ) or ivermectin (IVM) on 18 sheep farms. Two samples were collected from each group: on day zero (T1) and 10-14 days after treatment. Faecal egg counts (eggs per gramme, EPG) were determined using a modified McMaster technique. Animals with < 140 EPG on day zero were removed from the analysis. The prevalence of AR was estimated using the in vivo faecal egg count reduction test. AR to FBZ was detected on three of 15 farms where FBZ was used (20 %) and was suspected on one farm (6.7 %). AR to IVM was detected on two of 16 farms where IVM was used (12.5 %). The main species of resistant gastrointestinal nematodes (GINs) identified after treatment were Teladorsagia spp. and Trichostrongylus spp. A questionnaire surveying 71 sheep farmers estimated that 71.8 % of sheep farmers used anthelmintics against GINs. IVM was the most frequently (68.6 %) applied anthelmintic, and 62.7 % of the respondents reported treating their animals twice a year. This study confirmed the presence of AR to GIN infections on sheep farms in Lithuania. Future studies should assess the prevalence of AR to GIN infection using in vitro methods.

scholarly journals Nematophagous Activity of Duddingtonia Flagrans MUCL 9827 Against Sheep Gastrointestinal Nematodes

2016 ◽  
Vol 65 (3-4) ◽  
pp. 13-20 ◽  
Author(s):  
Stanislav Simin ◽  
Simonida Đurić ◽  
Ljiljana Kuruca ◽  
Timea Hajnal-Jafari ◽  
Dragana Stamenov ◽  
...  
Keyword(s):  
Production Systems ◽  
Anthelmintic Resistance ◽  
Direct Interaction ◽  
Poor Performance ◽  
Gastrointestinal Nematodes ◽  
Fungal Species ◽  
Parasitic Nematodes ◽  
Current Experiment ◽  
Duddingtonia Flagrans ◽  
Reduction Percentage

Summary Gastro-intestinal nematodes (GIN) of sheep are one of major constraints in grazing production systems worldwide. Control is commonly achieved using anthelmintics, but global occurrence of anthelmintic resistance to different drugs and the emergence of multi-resistant GIN species seriously limit the efficiency of their use. Therefore, integrated parasite management is widely recommended, with nematophagous fungi as one of control tools. Duddingtonia flagrans is one of the most used species, with various effect of different isolates. In previously performed coproculture assay, we showed low efficacy of D. flagrans MUCL 9827 against infective larvae (L3) of sheep GIN. The aim of current experiment was to reevaluate its nematophagous potential, using the medium where direct interaction between the fungus and L3 could be observed. Nematophagous activity was tested on 2% water agar with addition of chloramphenicol on three series of plates seeded with 500 and 1000 chlamidospores and agar blocks with 7 days old mycelium. At Days 0 and 5, 500 L3 of sheep GIN were added to test the trapping activity. The cultures, including control plates with only L3, were incubated at 25°C for 10 days, followed by evaluation of their number and reduction percentage. Nematophagous activity of D. flagrans MUCL 9827 against L3 was clearly demonstrated. However, the overall efficacy was poor since trapping was observed only in one out of nine plates containing fungal material. Potential reasons for such poor performance of the isolate of fungal species, otherwise known as successful in trapping animal parasitic nematodes, are discussed.

scholarly journals Increased Expression of a MicroRNA Correlates with Anthelmintic Resistance in Parasitic Nematodes

2017 ◽  
Vol 7 ◽  
Author(s):  
Victoria Gillan ◽  
Kirsty Maitland ◽  
Roz Laing ◽  
Henry Gu ◽  
Neil D. Marks ◽  
...  
Keyword(s):  
Anthelmintic Resistance ◽  
Parasitic Nematodes

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 &ldquo;cycle of discovery&rdquo;, 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.

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