Caenorhabditis elegans: how good a model for veterinary parasites?

Geary, Timothy G.; Thompson, David P.

doi:10.1016/s0304-4017(01)00562-3

Cited by 114 publications

(86 citation statements)

References 77 publications

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“…There are inevitable limitations of using a free-living nematode to replicate parasitic nematode systems, for example there is no recognition of the complexity of the infectious process (Geary and Thompson, 2001). The in vitro C. elegans assay has not produced valuable new leads since its development (Geary et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

In vitro anthelmintic, antibacterial and cytotoxic effects of extracts from plants used in South African ethnoveterinary medicine

McGaw

Merwe

Eloff

2007

The Veterinary Journal

133

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Many plants are used for ethnoveterinary purposes in South Africa, particularly in rural areas. Extracts of 17 plant species employed to treat infectious diseases were prepared using three solvents and the antibacterial activity of the extracts was determined against two Gram-positive and two Gram-negative bacteria. Anthelmintic activity was evaluated against the free-living nematode Caenorhabditis elegans and toxicity was determined using the brine shrimp larval mortality test. Most of the plant extracts demonstrated antibacterial activity, with the best minimum inhibitory concentration (MIC) being 0.1 mg mL −1 . More than a third of the extracts displayed anthelmintic activity. Toxic effects against brine shrimp larvae were shown by 30% of extracts, with the lowest LC 50 recorded as 0.6 mg mL −1 . The promising biological activity displayed by a number of plant extracts supports the ethnoveterinary use of these plants but in vivo tests are required to ascertain fully their medicinal properties and potential toxicity.

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Section: Discussionmentioning

confidence: 99%

In vitro anthelmintic, antibacterial and cytotoxic effects of extracts from plants used in South African ethnoveterinary medicine

McGaw

Merwe

Eloff

2007

The Veterinary Journal

133

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“…Importantly, all of the commercially available anthelminthics also appear to be effective against C. elegans [12,43]. However, nematodes exhibit enormous diversity and it is not clear whether pathways or receptors identified in C. elegans will faithfully translate to parasitic species.…”

Section: Discussionmentioning

confidence: 99%

“…Because of the enormous variation among species of nematodes, processes in C. elegans may not be exactly duplicated in parasitic nematodes and binding constants and regulation may differ significantly among orthologous nematode proteins. On the positive side, all of anthelminthics currently in use appear to function similarly in both C. elegans and parasitic nematodes [12].…”

Section: Introductionmentioning

confidence: 99%

Are Caenorhabditis elegans receptors useful targets for drug discovery: Pharmacological comparison of tyramine receptors with high identity from C. elegans (TYRA-2) and Brugia malayi (Bm4)

Smith

Rex

Komuniecki

2007

Molecular and Biochemical Parasitology

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The biogenic amine, tyramine (TA), modulates a number of key processes in nematodes and a number of TA-specific receptors have been identified. In the present study we have identified a putative TA receptor (Bm4) in the recently completed Brugia malayi genome and compared its pharmacology to its putative C. elegans orthologue, TYRA-2, under identical expression and assay conditions. TYRA-2 and Bm4 are the most closely related C. elegans and B. malayi BA receptors and differ by only 14 aa in the TM regions directly involved in ligand binding. Membranes from HEK-293 cells stably expressing Bm4 exhibited specific, saturable, high-affinity, [ 3 H]LSD and [ 3 H]TA binding with K d s of 18.1 ± 0.93 nM and 15.1 ± 0.2 nM, respectively. More importantly, both TYRA-2 and Bm4 TA exhibited similar rank orders of potencies for a number of potential tyraminergic ligands. However, some significant differences were noted. For example, chloropromazine exhibited an order of magnitude higher affinity for Bm4 than TYRA-2 (pK i s of 7.6 ± 0.2 and 6.49 ± 0.1, respectively). In contrast, TYRA-2 had significantly higher affinity for phentolamine than Bm4. These results highlight the utility of the nearly completed B. malayi genome and the importance of using receptors from individual parasitic nematodes for drug discovery.

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“…The choice of C. elegans for this role is justified by its long history as a model organism for anthelmintic discovery. 23,24 Testing tens of thousands of random compounds requires an assay capable of relatively high throughput. The most obvious phenotype associated with reduced sel-12 function in C. elegans is diminished egg laying (the egl phenotype), although the product of this gene is also required for morphology and function of thermosensory neurons in C. elegans.…”

Section: Discussionmentioning

confidence: 99%

Screening for Presenilin Inhibitors Using the Free-Living Nematode, Caenorhabditis elegans

Ellerbrock¹,

Coscarelli²,

Gurney³

et al. 2004

SLAS Discovery

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Caenorhabditis elegans contains 3 homologs of presenilin genes that are associated with Alzheimer's disease. Loss-offunction mutations in C. elegans genes cause a defect in egg laying. In humans, loss of presenilin-1 (PS1) function reduces amyloid-beta peptide processing from the amyloid protein precursor. Worms were screened for compounds that block egg laying, phenocopying presenilin loss of function. To accommodate even relatively high throughput screening, a semiautomated method to quantify egg laying was devised by measuring the chitinase released into the culture medium. Chitinase is released by hatching eggs, but little is shed into the medium from the body cavity of a hermaphrodite with an egg laying deficient (egl) phenotype. Assay validation involved measuring chitinase release from wild-type C. elegans (N2 strain), sel-12 presenilin loss-of-function mutants, and 2 strains of C. elegans with mutations in the egl-36 K + channel gene. Failure to find specific presenilin inhibitors in this collection likely reflects the small number of compounds tested, rather than a flaw in screening strategy. Absent defined biochemical pathways for presenilin, this screening method, which takes advantage of the genetic system available in C. elegans and its historical use for anthelminthic screening, permits an entry into mechanismbased discovery of drugs for Alzheimer's disease. (Journal of Biomolecular Screening 2004:147-152)

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Caenorhabditis elegans: how good a model for veterinary parasites?

Cited by 114 publications

References 77 publications

In vitro anthelmintic, antibacterial and cytotoxic effects of extracts from plants used in South African ethnoveterinary medicine

In vitro anthelmintic, antibacterial and cytotoxic effects of extracts from plants used in South African ethnoveterinary medicine

Are Caenorhabditis elegans receptors useful targets for drug discovery: Pharmacological comparison of tyramine receptors with high identity from C. elegans (TYRA-2) and Brugia malayi (Bm4)

Screening for Presenilin Inhibitors Using the Free-Living Nematode, Caenorhabditis elegans

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