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Unfortunately, most of these drugs have a limited single-dose efficacy against infections caused by the whipworm,\n                    <jats:italic>Trichuris<\/jats:italic>\n                    . These infections are of both human and veterinary importance. However, in contrast to a wide range of parasitic nematode species, the narrow-spectrum anthelmintic oxantel has a high efficacy on\n                    <jats:italic>Trichuris spp<\/jats:italic>\n                    . Despite this knowledge, the molecular target(s) of oxantel within\n                    <jats:italic>Trichuris<\/jats:italic>\n                    is still unknown. In the distantly related pig roundworm,\n                    <jats:italic>Ascaris suum<\/jats:italic>\n                    , oxantel has a small, but significant effect on the recombinant homomeric Nicotine-sensitive ionotropic acetylcholine receptor (\n                    <jats:italic>N<\/jats:italic>\n                    -AChR) made up of five ACR-16 subunits. Therefore, we hypothesized that in whipworms, a putative homolog of an ACR-16 subunit, can form a functional oxantel-sensitive receptor. Using the pig whipworm\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>suis<\/jats:italic>\n                    as a model, we identified and cloned a novel ACR-16-like subunit and successfully expressed the corresponding homomeric channel in\n                    <jats:italic>Xenopus laevis<\/jats:italic>\n                    oocytes. Electrophysiological experiments revealed this receptor to have distinctive pharmacological properties with oxantel acting as a full agonist, hence we refer to the receptor as an\n                    <jats:italic>O<\/jats:italic>\n                    -AChR subtype. Pyrantel activated this novel\n                    <jats:italic>O<\/jats:italic>\n                    -AChR subtype moderately, whereas classic nicotinic agonists surprisingly resulted in only minor responses. We observed that the expression of the ACR-16-like subunit in the free-living nematode\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    conferred an increased sensitivity to oxantel of recombinant worms. We demonstrated that the novel\n                    <jats:italic>Tsu-<\/jats:italic>\n                    ACR-16-like receptor is indeed a target for oxantel, although other receptors may be involved. These finding brings new insight into the understanding of the high sensitivity of whipworms to oxantel, and highlights the importance of the discovery of additional distinct receptor subunit types within\n                    <jats:italic>Trichuris<\/jats:italic>\n                    that can be used as screening tools to evaluate the effect of new synthetic or natural anthelmintic compounds.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1008982","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T23:48:02Z","timestamp":1612741682000},"page":"e1008982","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["The narrow-spectrum anthelmintic oxantel is a potent agonist of a novel acetylcholine receptor subtype in whipworms"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2744-3093","authenticated-orcid":true,"given":"Tina V. A.","family":"Hansen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8105-1579","authenticated-orcid":true,"given":"Susanna","family":"Cirera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Neveu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Courtot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0596-6598","authenticated-orcid":true,"given":"Claude L.","family":"Charvet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-7938","authenticated-orcid":true,"given":"Kirstine","family":"Calloe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan A.","family":"Klaerke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"issue":"6671","key":"ppat.1008982.ref001","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/32160","article-title":"A molecular evolutionary framework for the phylum Nematoda","volume":"392","author":"ML Blaxter","year":"1998","journal-title":"Nature"},{"issue":"10159","key":"ppat.1008982.ref002","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 Diseases and Injuries for 195 countries and territories, 1990\u20132017:A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"SL James","year":"2018","journal-title":"Lancet"},{"key":"ppat.1008982.ref003","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1017\/S0031182000006491","article-title":"Malnutrition and parasitic helminth infections","volume":"121","author":"LS Stephenson","year":"2000","journal-title":"Parasitology"},{"issue":"Suppl 1","key":"ppat.1008982.ref004","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1740-8709.2007.00127.x","article-title":"A review and meta-analysis of the impact of intestinal worms on child growth and nutrition.","volume":"4","author":"A Hall","year":"2008","journal-title":"Matern Child Nutr"},{"issue":"16","key":"ppat.1008982.ref005","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1001\/jama.299.16.1937","article-title":"Efficacy of current drugs against soil-transmitted helminth infections:systematic review and meta-analysis","volume":"299","author":"J Keiser","year":"2008","journal-title":"JAMA"},{"issue":"1","key":"ppat.1008982.ref006","first-page":"35","article-title":"Macatangay BJC. 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