Publications by authors named "Roz Laing"

Sulphite oxidase has an essential role in detoxifying environmental and endogenously generated sulphite into sulphate and requires the molybdenum cofactor (Moco) to function. Until recently it was believed that the synthesis pathway for Moco was so important for survival that it was conserved in all multicellular animals. Here we report the use of comparative genomics to identify the absence of the first enzyme involved in Moco synthesis in Haemonchus contortus, a highly pathogenic and economically important helminth of livestock that, similar to many parasitic nematode species, has proved difficult to maintain in vitro.

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The bovine lungworm, (Bloch, 1782), is highly pathogenic and disease outbreaks can be difficult to predict and manage. Rapid and accurate diagnosis is vital, but without a sensitive diagnostic test this remains challenging in clinical practice. High performance molecular detection tools are therefore required to improve the diagnosis of this parasite and promote the implementation of strategic control measures.

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Background: The bovine lungworm Dictyocaulus viviparus negatively impacts bovine health and leads to substantial economic losses. Lungworm infections can be difficult to manage due to the unpredictable and severe nature of clinical outbreaks. Despite the widespread use of macrocyclic lactones (MLs) in grazing cattle in the UK, there have been no confirmed reports of resistant lungworms to date, with only one case of anthelmintic-resistant (ML) lungworm confirmed worldwide.

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  • A variant called S168T in the ACR-8 subunit of acetylcholine receptors has been linked to resistance against the drug levamisole in the parasitic worm Haemonchus contortus.
  • Using a specialized system involving Xenopus laevis oocytes and voltage-clamp techniques, researchers found that the S168T variant decreased the response of the L-AChR-1.1 receptor to levamisole, making it less effective.
  • These findings indicate that the S168T mutation is crucial in understanding how levamisole resistance occurs at the receptor level.
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Haemonchus contortus is a parasitic haematophagous nematode that primarily affects small ruminants and causes significant economic loss to the global livestock industry. Treatment of haemonchosis typically relies on broad-spectrum anthelmintics, resistance to which is an important cause of treatment failure. Resistance to levamisole remains less widespread than to other major anthelmintic classes, prompting the need for more effective and accurate surveillance to maintain its efficacy.

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  • Anthelmintic-resistant nematodes threaten livestock production, making early detection of resistance critical to minimize losses.
  • A new mixed deep amplicon sequencing method has been developed for detecting genes associated with resistance in parasitic worms, marking a first in veterinary diagnostics across multiple drug types and worm species.
  • In Australian field isolates, levamisole resistance was less common than benzimidazole resistance, indicating levamisole remains effective for small ruminants in New South Wales.
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  • Understanding how parasites survive and affect host immune responses is key for improving disease management and developing new treatments.
  • Traditional methods like microarray and RNA sequencing give insights into gene expression during parasite development but miss details about different cell types and their organization.
  • Single-cell RNA sequencing (scRNA-seq) provides a deeper look at gene expression in individual cells and can be complemented by using organoids to study host-parasite interactions and parasite growth in a lab setting.
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  • Parasitic helminths, like other pathogens, can quickly develop resistance to drugs, making it crucial to understand the genetics behind this resistance, especially in nematodes.
  • This study used genetic crosses in natural hosts to map resistance genes for major classes of anthelmintics, identifying new alleles linked to resistance against benzimidazoles, levamisole, and ivermectin.
  • The findings pinpoint the gene cky-1 as significant for ivermectin survival, providing a pathway for developing molecular diagnostics to address drug resistance in parasitic infections.
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Genome-wide methods offer a powerful approach to detect signatures of drug selection. However, limited availability of suitable reference genomes and the difficulty of obtaining field populations with well-defined, distinct drug treatment histories mean there is little information on the signatures of selection in parasitic nematodes and on how best to detect them. This study addresses these knowledge gaps by using field populations of Haemonchus contortus with well-defined benzimidazole treatment histories, leveraging a recently completed chromosomal-scale reference genome assembly.

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Background: Guidelines for sustainable use of moxidectin were established in 2020. This study aimed to identify how Scottish sheep farmers are using this key endectocide and estimate its effectiveness against gastrointestinal nematodes.

Methods: Questionnaires were distributed to sheep farmers across Scotland, and analysis focused on moxidectin use in relation to Sustainable Control of Parasites in Sheep (SCOPS) guidelines.

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Article Synopsis
  • Haemonchus contortus is a blood-sucking parasitic worm that affects small ruminants, causing health and economic issues globally, with resistance to common treatments becoming a major problem.
  • Levamisole (LEV) is a key treatment option, as it has lower resistance rates; it works by binding to acetylcholine receptors in the worms, leading to paralysis.
  • Recent studies have identified a specific genetic change (S168T) in the acr-8 gene associated with LEV resistance; an optimized PCR test was developed to detect this variant, showing its prevalence in resistant populations and its potential use for diagnosing LEV resistance in the field.
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  • Ivermectin is crucial for global health in humans and animals, but resistance to the drug is widespread in parasites, raising concerns about treatment effectiveness.
  • Despite extensive research, the genetic basis for this resistance in parasitic helminths remains poorly understood due to their complex genomes and evolutionary factors.
  • A genetic study of Haemonchus contortus revealed that resistant populations exhibit specific gene expression changes linked to ivermectin resistance, including upregulation of key genes involved in neuronal function and cellular processes.
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Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Here, we report using PacBio long-read and OpGen and 10X Genomics long-molecule methods to generate a highly contiguous 283.4 Mbp chromosome-scale genome assembly including a resolved sex chromosome for the MHco3(ISE).

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  • Small RNAs, such as microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), and small interfering RNAs (siRNAs), are key regulators of gene expression and are found in various organisms, including parasitic nematodes.
  • Research using genome data and small RNA sequencing has revealed the expression patterns of these small RNAs during different lifecycle stages of nematodes and their potential roles in regulating gene expression in both the parasites and their hosts.
  • The review highlights how miRNAs influence development in nematodes and suggests that piRNAs and siRNAs help suppress certain genes, with advancements in RNA interference continuing to enhance our understanding of these small RNAs' functions.
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  • Parasitic nematodes, like Haemonchus contortus, shift between free-living and parasitic stages, and understanding how this transition is controlled is still not fully understood.
  • This study identified two specific microRNAs (mir-228 and mir-235) that are crucial during the infective larval stage and may help maintain the nematodes in an arrested development state.
  • The research suggests that these miRNAs interact with insulin signaling pathways to regulate growth and could be targeted for potential therapies to manage parasitic infections.
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Recent reports of monepantel (MPTL) resistance in UK field isolates of Teladorsagia circumcincta has highlighted the need for a better understanding of the mechanism of MPTL-resistance in order to preserve its anthelmintic efficacy in this economically important species. Nine discrete populations of T. circumcincta were genotypically characterised; three MPTL-susceptible isolates, three experimentally selected MPTL-resistant strains and three field derived populations.

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  • Whole-genome sequencing is increasingly used to study helminth genomes, focusing on genome assembly, population genetics, and diagnostics, but adult parasites are difficult to access for DNA sampling.
  • The study explores five low-input DNA extraction methods along with a sequencing protocol to enable whole-genome sequencing of immature helminth stages, which typically yield low DNA quantities and face contamination issues.
  • Results showed successful sample preparations for most tested species, indicating that whole-genome sequencing of individual helminth parasites is feasible and can enhance diagnostic and surveillance efforts.
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  • The study examines how genetic diversity in the parasitic nematode Haemonchus contortus can impact differential expression analyses, which are used to identify genes linked to drug resistance and other traits.* -
  • Researchers discovered that high sequence polymorphism can lead to inaccuracies in mapping RNAseq reads, resulting in misleading estimates of gene expression differences between strains.* -
  • By optimizing mapping techniques and filtering out highly polymorphic genes, the study revealed over 824 genuinely differentially expressed genes, emphasizing the complex relationship between genetic variation and observable traits, particularly in regard to potential drug resistance.*
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Anthelmintic resistance is a threat to global food security. In order to alleviate the selection pressure for resistance and maintain drug efficacy, management strategies increasingly aim to preserve a proportion of the parasite population in 'refugia', unexposed to treatment. While persuasive in its logic, and widely advocated as best practice, evidence for the ability of refugia-based approaches to slow the development of drug resistance in parasitic helminths is currently limited.

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  • Helminths cause significant disease in animals and plants, with widespread use of anthelmintics leading to resistance, raising concerns for livestock and human health.
  • A genome-wide analysis of the nematode Haemonchus contortus shows a key genomic region on chromosome V linked to ivermectin resistance, indicating a possible new mechanism of resistance.
  • Strong selection for the resistant allele at this locus was documented, highlighting the complexity of resistance evolution despite limited genetic resolution.
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UDP-glycosyltransferases (UGT), catalysing conjugation of UDP-activated sugar donors to small lipophilic chemicals, are widespread in living organisms from bacteria to fungi, plant, or animals. The progress of genome sequencing has enabled an assessment of the UGT multigene family in Haemonchus contortus (family Trichostrongylidae, Nematoda), a hematophagous gastrointestinal parasite of small ruminants. Here we report 32 putative UGT genes divided into 15 UGT families.

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  • Ovine parasitic gastroenteritis, primarily caused by the pathogen Teladorsagia circumcincta, is commonly treated with anthelmintics such as benzimidazole and ivermectin, yet resistance to these treatments is a growing concern.
  • A study on a commercial sheep farm in southeast Scotland revealed moderate resistance levels, with a faecal egg count reduction test showing only 65% efficacy for albendazole and 77% for ivermectin.
  • Further analysis indicated that the removal of susceptible species post-treatment masked the presence of a highly resistant T. circumcincta population, and genetic testing confirmed a significant occurrence of resistance-associated mutations.
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Some nematode species are economically important parasites of livestock, while others are important human pathogens causing some of the most important neglected tropical diseases. In both humans and animals, anthelmintic drug administration is the main control strategy, but the emergence of drug-resistant worms has stimulated the development of alternative control approaches. Among these, vaccination is considered to be a sustainable and cost effective strategy.

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Article Synopsis
  • The nematode Haemonchus contortus significantly impacts small ruminant health and agriculture due to its resistance to anthelmintic drugs, posing challenges for livestock sustainability worldwide.
  • Researchers conducted a genetic cross between two strains to create a chromosome-scale genetic map, revealing insights into the genome's variation, recombination rates, and polyandry affecting progeny genetics.
  • The study advances our understanding of parasitic helminth genetics and resistance, emphasizing the potential of whole-genome resequencing for mapping genetic traits in non-model organisms.
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  • Resistance to anthelmintic drugs poses a significant challenge in treating parasitic nematodes affecting humans and animals, with mutations in drug target genes and changes in gene expression contributing to this problem.
  • This study investigates the role of microRNAs (miRNAs) in drug-resistant nematodes, revealing that a specific miRNA is significantly upregulated in multiple ivermectin-resistant strains compared to susceptible ones, and is enriched in female worms.
  • By identifying potential mRNA targets of this miRNA through computational analysis and experimental validation, the research highlights the importance of miRNAs in mediating drug resistance and suggests their potential as biomarkers for nematode resistance.
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