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Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans

Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans
Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans
Emodepside, a cyclooctadepsipeptide, is a broad-spectrum anthelmintic previously shown to paralyse body wall muscle and pharyngeal muscle in the model nematode Caenorhabditis elegans. We demonstrate that wild-type C. elegans L4 are less sensitive than adults to emodepside in two independent assays of locomotor behaviour: body bend generation on agar (adult IC50 3.7 nM, L4 IC50 13.4 nM) and thrashing behaviour in liquid (thrashing behaviour as a % of controls after 1 h in 10 É M emodepside: adults 16%, L4 worms 48%). We also show that continuous exposure of wild-type C. elegans to emodepside throughout the life-cycle from egg onwards, slows worm development, an effect that is emodepside concentration-dependent. The rate of worm-hatching from eggs on agar plates containing emodepside was not significantly different from controls, suggesting that it is development post-hatching rather than hatching itself that is affected by the drug. Emodepside also inhibits wild-type C. elegans egg-laying, with acute exposure to the drug at 500 nM resulting in an almost total inhibition within the first hour. However, the rate of egg production was not inhibited and therefore emodepside-treated worms became bloated with eggs, eventually rupturing. This suggests that the effect of emodepside on reproduction is not due to an inhibition of egg production but rather a paralytic effect on the egg-laying muscles. These results, when coupled with previous research, suggest that emodepside interferes with signalling at the neuromuscular junction on the body-wall muscles (Willson et al., 2003), pharynx (Willson et al., 2004) and egg-laying muscles and thus inhibits three important physiological functions: locomotion, feeding and reproduction.
0020-7519
627-636
Bull, Kathryn
fd07202e-8fa2-419f-80ec-ba8e2a4db8b1
Cook, Alan
7b75a288-b189-4c85-8122-0f389847ac4a
Hopper, Neil A.
d2aed184-733b-47f6-8d74-fa1633ae6cf0
Harder, Achim
6bcbaba4-2209-45eb-a29f-5f1ac4476fa2
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Walker, Robert J.
9368ac2d-f1e9-4bd9-a4b4-4a161c4aa140
Bull, Kathryn
fd07202e-8fa2-419f-80ec-ba8e2a4db8b1
Cook, Alan
7b75a288-b189-4c85-8122-0f389847ac4a
Hopper, Neil A.
d2aed184-733b-47f6-8d74-fa1633ae6cf0
Harder, Achim
6bcbaba4-2209-45eb-a29f-5f1ac4476fa2
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Walker, Robert J.
9368ac2d-f1e9-4bd9-a4b4-4a161c4aa140

Bull, Kathryn, Cook, Alan, Hopper, Neil A., Harder, Achim, Holden-Dye, Lindy and Walker, Robert J. (2006) Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans. International Journal for Parasitology, 37 (6), 627-636. (doi:10.1016/j.ijpara.2006.10.013).

Record type: Article

Abstract

Emodepside, a cyclooctadepsipeptide, is a broad-spectrum anthelmintic previously shown to paralyse body wall muscle and pharyngeal muscle in the model nematode Caenorhabditis elegans. We demonstrate that wild-type C. elegans L4 are less sensitive than adults to emodepside in two independent assays of locomotor behaviour: body bend generation on agar (adult IC50 3.7 nM, L4 IC50 13.4 nM) and thrashing behaviour in liquid (thrashing behaviour as a % of controls after 1 h in 10 É M emodepside: adults 16%, L4 worms 48%). We also show that continuous exposure of wild-type C. elegans to emodepside throughout the life-cycle from egg onwards, slows worm development, an effect that is emodepside concentration-dependent. The rate of worm-hatching from eggs on agar plates containing emodepside was not significantly different from controls, suggesting that it is development post-hatching rather than hatching itself that is affected by the drug. Emodepside also inhibits wild-type C. elegans egg-laying, with acute exposure to the drug at 500 nM resulting in an almost total inhibition within the first hour. However, the rate of egg production was not inhibited and therefore emodepside-treated worms became bloated with eggs, eventually rupturing. This suggests that the effect of emodepside on reproduction is not due to an inhibition of egg production but rather a paralytic effect on the egg-laying muscles. These results, when coupled with previous research, suggest that emodepside interferes with signalling at the neuromuscular junction on the body-wall muscles (Willson et al., 2003), pharynx (Willson et al., 2004) and egg-laying muscles and thus inhibits three important physiological functions: locomotion, feeding and reproduction.

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Published date: 27 November 2006

Identifiers

Local EPrints ID: 43902
URI: http://eprints.soton.ac.uk/id/eprint/43902
ISSN: 0020-7519
PURE UUID: 596f1fb7-67c7-468b-afec-0602094add0c
ORCID for Lindy Holden-Dye: ORCID iD orcid.org/0000-0002-9704-1217
ORCID for Robert J. Walker: ORCID iD orcid.org/0000-0002-9031-7671

Catalogue record

Date deposited: 06 Feb 2007
Last modified: 03 Dec 2019 02:07

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