{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:56:50Z","timestamp":1787029010137,"version":"build-2736575974"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G051812N"],"award-info":[{"award-number":["G051812N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["12I0317N"],"award-info":[{"award-number":["12I0317N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007660","name":"Universiteit Antwerpen","doi-asserted-by":"publisher","award":["TT-ZAPBOF 33049"],"award-info":[{"award-number":["TT-ZAPBOF 33049"]}],"id":[{"id":"10.13039\/501100007660","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Current treatment options for visceral leishmaniasis have several drawbacks, and clinicians are confronted with an increasing number of treatment failures. To overcome this, the Drugs for Neglected Diseases initiative (DNDi) has invested in the development of novel antileishmanial leads, including a very promising class of oxaboroles. The mode of action\/resistance of this series to Leishmania is still unknown and may be important for its further development and implementation. Repeated in vivo drug exposure and an in vitro selection procedure on both extracellular promastigote and intracellular amastigote stages were both unable to select for resistance. The use of specific inhibitors for ABC-transporters could not demonstrate the putative involvement of efflux pumps. Selection experiments and inhibitor studies, therefore, suggest that resistance to oxaboroles may not emerge readily in the field. The selection of a genome-wide cosmid library coupled to next-generation sequencing (Cos-seq) was used to identify resistance determinants and putative targets. This resulted in the identification of a highly enriched cosmid, harboring genes of chromosome 2 that confer a subtly increased resistance to the oxaboroles tested. Moderately enriched cosmids encompassing a region of chromosome 34 contained the cleavage and polyadenylation specificity factor (cpsf) gene, encoding the molecular target of several related benzoxaboroles in other organisms.<\/jats:p>","DOI":"10.3390\/microorganisms9071408","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:52:46Z","timestamp":1624963966000},"page":"1408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification of Resistance Determinants for a Promising Antileishmanial Oxaborole Series"],"prefix":"10.3390","volume":"9","author":[{"given":"Magali","family":"Van den Kerkhof","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Leprohon","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie du Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3530-0567","authenticated-orcid":false,"given":"Dorien","family":"Mabille","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hendrickx","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay B.","family":"Tulloch","sequence":"additional","affiliation":[{"name":"The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Wall","sequence":"additional","affiliation":[{"name":"The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Wyllie","sequence":"additional","affiliation":[{"name":"The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Chatelain","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi), 1202 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Mowbray","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi), 1202 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Braillard","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi), 1202 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ouellette","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie du Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-9509","authenticated-orcid":false,"given":"Louis","family":"Maes","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4870-3202","authenticated-orcid":false,"given":"Guy","family":"Caljon","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.jinf.2014.07.016","article-title":"Leishmaniasis","volume":"69","author":"Pace","year":"2014","journal-title":"J. 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