Silencing of essential genes by RNA interference in<i>Haemonchus contortus</i>

Zawadzki, Jody L.; Kotze, Andrew C.; Fritz, Julie-Anne; Johnson, Nick; Hemsworth, J E; Hines, Barney M.; Behm, Carolyn A.

doi:10.1017/s0031182012000121

Cited by 41 publications

(32 citation statements)

References 55 publications

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“…12 First-, second-, and third-stage larvae (L1s, L2s, and iL3s) were produced by incubating eggs at 27°C for 1, 4, and 7 days, respectively, and then concentrated using a Baermann funnel technique. 12 Fourth-stage larvae (L4s) and adults were collected from the abomasa from goats at 8 days and 1 month, respectively, following infection and extensively washed; males and females were separated. Individual developmental stages of H. contortus were snapfrozen in liquid nitrogen and then stored at −80°C until use.…”

Section: Procurement Of C Elegans Andmentioning

confidence: 99%

A serine/threonine‐specific protein kinase ofHaemonchus contortuswith a role in the development

Gasser

et al. 2019

FASEB j.

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In the free‐living nematode Caenorhabditis elegans, the serine/threonine‐specific protein kinase, AKT, is known to play a key role in dauer formation, life‐span, and stress‐resistance through the insulin‐like signaling pathway. Although the structure and function of AKT‐coding genes of C. elegans are understood, this is not the case for homologous genes in parasitic nematodes. In the present study, we explored a C. elegans akt‐1 gene homolog in the parasitic nematode Haemonchus contortus, investigated its transcript isoforms (Hc‐akt‐1a and Hc‐akt‐1b), and studied expression and function using both homologous and heterologous functional genomic tools. In C. elegans, we showed that the predicted promoter of Hc‐akt‐1 drives substantial expression in ASJ neurons of the N2 (wild‐type) strain. In H. contortus (Haecon‐5 stain), RNAi (soaking) led to a significantly decreased transcript abundance for both Hc‐akt‐1a and Hc‐akt‐1b, and reduced larval development in larval stages in vitro. Chemical inhibition was also shown to block larval development. Taken together, the evidence from this study points to a key functional role for Hc‐akt‐1 in H. contortus.

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Section: Procurement Of C Elegans Andmentioning

confidence: 99%

A serine/threonine‐specific protein kinase ofHaemonchus contortuswith a role in the development

Gasser

et al. 2019

FASEB j.

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“…In some cases, reduced target transcript levels were correlated with phenotypic changes in the subject parasitic nematodes. However, overall, RNAi effects on animal parasitic nematodes have been inconsistent, with variable results obtained between subject species, target genes, and experiments [137][138][139][140]. RNAi is apparently more efficient as an experimental tool in plant parasitic nematodes than in animal parasitic nematodes [138,141].…”

Section: Rna Interferencementioning

confidence: 99%

Advances in the Molecular and Cellular Biology of Strongyloides spp.

Jaleta

Lok

2019

Curr Trop Med Rep

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Purpose of Review This paper constitutes an update of recent studies on the general biology, molecular genetics, and cellular biology of Strongyloides spp. and related parasitic nematodes. Recent Findings Increasingly, human strongyloidiasis is considered the most neglected of neglected tropical diseases. Despite this, the last 5 years has seen remarkable advances in the molecular biology of Strongyloides spp. Genome sequences for S. stercoralis, S. ratti, S. venezuelensis, S. papillosus, and the related parasite Parastrongyloides trichosuri were created, annotated, and analyzed. These genomic resources, along with a practical transgenesis platform for Strongyloides spp., aided a major achievement, the advent of targeted mutagenesis via CRISPR/Cas9 in S. stercoralis and S. ratti. The genome sequences have also enabled significant molecular epidemiologic and phylogenetic findings on human strongyloidiasis, including the first genetic evidence of zoonotic transmission of S. stercoralis between dogs and humans. Studies of molecular signaling pathways identified the nuclear receptor Ss-DAF-12 as one that can be manipulated in the parasite by exogenous application of its steroid ligands. The chemotherapeutic implications of this were unscored by a study in which a Ss-DAF-12 ligand suppressed autoinfection by S. stercoralis in a new murine model of human strongyloidiasis. Summary Seminal advances in genomics of Strongyloides spp. have transformed research into strongyloidiasis, facilitating fundamental phylogenetic and epidemiologic studies and aiding the deployment of CRISPR/Cas9 gene disruption and editing as functional genomic tools in Strongyloides spp. Studies of Ss-DAF-12 signaling in S. stercoralis demonstrated the potential of this pathway as a novel chemotherapeutic target in parasitic nematodes.

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“…Although such rescue studies help to define specific gene function in H. contortus, direct parasite RNAi application will provide greater accuracy of identifying genes. Successful H. contortus RNAi has been reported in gene silencing (Geldhof et al, 2006;Zawadzki et al, 2012).…”

Section: Introductionmentioning

confidence: 99%