{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:27:28Z","timestamp":1760059648122,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","award":["R21AI166279"],"award-info":[{"award-number":["R21AI166279"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Multi-anthelmintic resistance in hookworms poses a significant challenge to both human and veterinary health, underscoring the need for novel treatment strategies. In this study, we evaluated the in vitro efficacy of three anthelmintics\u2014pyrantel, ivermectin, and emodepside\u2014against L3 larvae of drug-susceptible (WMD) and triple-anthelmintic-resistant (BCR) isolates of Ancylostoma caninum. While pyrantel was largely ineffective and ivermectin induced high mortality in both isolates, emodepside displayed a surprising trend: the drug-resistant BCR isolate was more susceptible than the drug-susceptible WMD isolate. To explore the underlying mechanism, we performed survival assays in the presence of penitrem A, a BK channel (SLO-1) inhibitor. The addition of penitrem A reversed the enhanced emodepside sensitivity in BCR, implicating elevated basal expression of SLO-1 channels as a potential factor. These findings suggest that emodepside, via its action on SLO-1, may offer a promising therapeutic avenue to combat multidrug-resistant hookworm infections.<\/jats:p>","DOI":"10.3390\/tropicalmed10070181","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T05:00:37Z","timestamp":1751259637000},"page":"181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Emodepside Efficacy in Drug-Resistant and Drug-Susceptible Ancylostoma caninum Highlights Variability in Potassium Channel Activity"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0010-6222","authenticated-orcid":false,"given":"Catherine A.","family":"Jackson","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5269-6649","authenticated-orcid":false,"given":"Elise L.","family":"McKean","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20052, USA"},{"name":"Department of Biological Sciences, The George Washington University, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-1413","authenticated-orcid":false,"given":"John M.","family":"Hawdon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1756-3305-7-37","article-title":"Global numbers of infection and disease burden of soil transmitted helminth infections in 2010","volume":"7","author":"Pullan","year":"2014","journal-title":"Parasites Vectors"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1186\/s13071-019-3828-6","article-title":"Multiple drug resistance in the canine hookworm Ancylostoma caninum: An emerging threat?","volume":"12","author":"Howell","year":"2019","journal-title":"Parasites Vectors"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ijpddr.2020.04.003","article-title":"Efficacy evaluation of anthelmintic products against an infection with the canine hookworm (Ancylostoma caninum) isolate Worthy 4.1F3P in dogs","volume":"13","author":"Mansour","year":"2020","journal-title":"Int. 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