{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T06:43:47Z","timestamp":1771915427330,"version":"3.50.1"},"reference-count":50,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T00:00:00Z","timestamp":1529452800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We here assessed the<jats:italic>in vitro<\/jats:italic>efficacy of the naptho-quinone buparvaquone (BPQ) against<jats:italic>Besnoitia besnoiti<\/jats:italic>tachyzoites<jats:italic>in vitro<\/jats:italic>. BPQ is currently licensed for the treatment of theileriosis in cattle in many countries, but not in the EU. In 4-day treatment assays, BPQ massively impaired tachyzoite proliferation with an IC<jats:sub>50<\/jats:sub>of 10 \u00b1 3 n<jats:sc>m<\/jats:sc>, and virtually complete inhibition was obtained in the presence of n<jats:sc>m<\/jats:sc>BPQ. Exposure to 1<jats:italic>\u00b5<\/jats:italic><jats:sc>m<\/jats:sc>BPQ leads to ultrastructural changes affecting initially the mitochondrial matrix and the cristae. After 96 h, most parasites were largely distorted, filled with cytoplasmic amylopectin granules and vacuoles containing components of unknown composition. Host cell mitochondria did not appear to be notably affected by the drug. However, upon prolonged exposure (14\u201316 days) to increased BPQ concentrations,<jats:italic>B. besnoiti<\/jats:italic>tachyzoites exhibited the capacity to adapt, and they resumed proliferation at dosages of up to 10<jats:italic>\u00b5<\/jats:italic><jats:sc>m<\/jats:sc>BPQ, albeit at a lower rate. These BPQ-adapted parasites maintained this lower susceptibility to BPQ treatment after freeze\u2013thawing, and inspection by the transmission electron microscopy revealed that they underwent proliferation in the absence of structurally intact mitochondria.<\/jats:p>","DOI":"10.1017\/s0031182018000975","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T06:31:41Z","timestamp":1529476301000},"page":"112-120","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":17,"title":["<i>In vitro<\/i>treatment of<i>Besnoitia besnoiti<\/i>with the naphto-quinone buparvaquone results in marked inhibition of tachyzoite proliferation, mitochondrial alterations and rapid adaptation of tachyzoites to increased drug concentrations"],"prefix":"10.1017","volume":"146","author":[{"given":"Joachim","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Manser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0622-2128","authenticated-orcid":false,"given":"Andrew","family":"Hemphill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2018,6,20]]},"reference":[{"key":"S0031182018000975_ref51","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.2460\/ajvr.1992.53.08.1396","article-title":"Efficacy of buparvaquone as a therapeutic and clearing agent of Babesia equi of European origin in horses","volume":"53","author":"Zaugg","year":"1992","journal-title":"American Journal of Veterinary Research"},{"key":"S0031182018000975_ref49","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-014-4035-1"},{"key":"S0031182018000975_ref47","doi-asserted-by":"crossref","first-page":"205","DOI":"10.21825\/vdt.v84i4.16596","article-title":"First confirmed case of bovine besnoitiosis in an imported bull in Belgium","volume":"84","author":"Vanhoudt","year":"2015","journal-title":"Vlaams Diergeneeskundig Tijdschrift"},{"key":"S0031182018000975_ref46","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2013.10.025"},{"key":"S0031182018000975_ref45","first-page":"259","article-title":"Besnoitia besnoiti: chemotherapeutic trials in vivo and in vitro","volume":"40","author":"Shkap","year":"1987b","journal-title":"Revue D'elevage Et De Medecine Veterinaire Des Pays Tropicaux"},{"key":"S0031182018000975_ref43","first-page":"289","article-title":"Chemotherapy of experimental Besnoitia besnoiti infection in rabbits","volume":"52","author":"Shkap","year":"1985","journal-title":"Onderstepoort Journal of Veterinary Research"},{"key":"S0031182018000975_ref42","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2012.01.016"},{"key":"S0031182018000975_ref40","doi-asserted-by":"publisher","DOI":"10.1136\/vr.103683"},{"key":"S0031182018000975_ref38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.03.010"},{"key":"S0031182018000975_ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2014.06.004"},{"key":"S0031182018000975_ref36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092929"},{"key":"S0031182018000975_ref34","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02324-16"},{"key":"S0031182018000975_ref33","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-016-0317-1"},{"key":"S0031182018000975_ref32","first-page":"16","article-title":"Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice","volume":"5","author":"M\u00fcller","year":"2015","journal-title":"International Journal for Parasitology: Drugs and Drug Resistance"},{"key":"S0031182018000975_ref31","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(75)80098-6"},{"key":"S0031182018000975_ref30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129678"},{"key":"S0031182018000975_ref29","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5288(18)31760-0"},{"key":"S0031182018000975_ref28","doi-asserted-by":"publisher","DOI":"10.1080\/00480169.2016.1204960"},{"key":"S0031182018000975_ref27","doi-asserted-by":"publisher","DOI":"10.1038\/nature14044"},{"key":"S0031182018000975_ref16","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182010000442"},{"key":"S0031182018000975_ref14","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-016-1405-9"},{"key":"S0031182018000975_ref35","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx134"},{"key":"S0031182018000975_ref24","doi-asserted-by":"publisher","DOI":"10.1024\/0036-7281\/a000389"},{"key":"S0031182018000975_ref26","doi-asserted-by":"publisher","DOI":"10.1038\/nature09022"},{"key":"S0031182018000975_ref5","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182014000262"},{"key":"S0031182018000975_ref11","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02297-16"},{"key":"S0031182018000975_ref20","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-7-20"},{"key":"S0031182018000975_ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2010.08.013"},{"key":"S0031182018000975_ref41","doi-asserted-by":"publisher","DOI":"10.1136\/amiajnl-2013-001700"},{"key":"S0031182018000975_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2011.01.027"},{"key":"S0031182018000975_ref19","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182000084754"},{"key":"S0031182018000975_ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2017.08.005"},{"key":"S0031182018000975_ref39","first-page":"265","article-title":"Studies on bovine besnoitiosis with special reference to the aetiology","volume":"28","author":"Pols","year":"1960","journal-title":"Onderstepoort Journal of Veterinary Research"},{"key":"S0031182018000975_ref48","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2017.01.001"},{"key":"S0031182018000975_ref44","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4017(87)90002-1"},{"key":"S0031182018000975_ref4","first-page":"3","article-title":"New concepts on the epidemiological features of bovine besnoitiosis as determined by laboratory and field investigations","volume":"35","author":"Bigalke","year":"1968","journal-title":"Onderstepoort Journal of Veterinary Research"},{"key":"S0031182018000975_ref9","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182011000114"},{"key":"S0031182018000975_ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2010.11.030"},{"key":"S0031182018000975_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2013.06.002"},{"key":"S0031182018000975_ref50","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01236-15"},{"key":"S0031182018000975_ref1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182013000383"},{"key":"S0031182018000975_ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2006.05.022"},{"key":"S0031182018000975_ref7","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182007002417"},{"key":"S0031182018000975_ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2007.03.003"},{"key":"S0031182018000975_ref10","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/30.6.827"},{"key":"S0031182018000975_ref12","doi-asserted-by":"publisher","DOI":"10.1645\/12-128.1"},{"key":"S0031182018000975_ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2013.04.023"},{"key":"S0031182018000975_ref15","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-1356(03)00154-5"},{"key":"S0031182018000975_ref17","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5288(91)90107-Y"},{"key":"S0031182018000975_ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2014.09.003"}],"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0031182018000975","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T16:02:07Z","timestamp":1720368127000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0031182018000975\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,20]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["S0031182018000975"],"URL":"https:\/\/doi.org\/10.1017\/s0031182018000975","relation":{},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,20]]},"assertion":[{"value":"Copyright \u00a9 Cambridge University Press 2018\u00a0","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}