{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T23:11:23Z","timestamp":1782688283457,"version":"3.54.5"},"reference-count":99,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Trypanosoma congolense<\/jats:italic>\n                    is a principal agent causing livestock trypanosomiasis in Africa, costing developing economies billions of dollars and undermining food security. Only the diamidine diminazene and the phenanthridine isometamidium are regularly used, and resistance is widespread but poorly understood. We induced stable diminazene resistance in\n                    <jats:italic>T. congolense<\/jats:italic>\n                    strain IL3000 in vitro. There was no cross\u2010resistance with the phenanthridine drugs, melaminophenyl arsenicals, oxaborole trypanocides, or with diamidine trypanocides, except the close analogs DB829 and DB75. Fluorescence microscopy showed that accumulation of DB75 was inhibited by folate. Uptake of [\n                    <jats:sup>3<\/jats:sup>\n                    H]\u2010diminazene was slow with low affinity and partly but reciprocally inhibited by folate and by competing diamidines. Expression of\n                    <jats:italic>T. congolense<\/jats:italic>\n                    folate transporters in diminazene\u2010resistant\n                    <jats:italic>Trypanosoma brucei brucei<\/jats:italic>\n                    significantly sensitized the cells to diminazene and DB829, but not to oxaborole AN7973. However, [\n                    <jats:sup>3<\/jats:sup>\n                    H]\u2010diminazene transport studies, whole\u2010genome sequencing, and RNA\u2010seq found no major changes in diminazene uptake, folate transporter sequence, or expression. Instead, all resistant clones displayed a moderate reduction in the mitochondrial membrane potential \u03a8m. We conclude that diminazene uptake in\n                    <jats:italic>T. congolense<\/jats:italic>\n                    proceed via multiple low affinity mechanisms including folate transporters; while resistance is associated with a reduction in \u03a8m it is unclear whether this is the primary cause of the resistance.\n                  <\/jats:p>","DOI":"10.1111\/mmi.14733","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T05:22:54Z","timestamp":1619846574000},"page":"564-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Diminazene resistance in\n                    <i>Trypanosoma congolense<\/i>\n                    is not caused by reduced transport capacity but associated with reduced mitochondrial membrane potential"],"prefix":"10.1111","volume":"116","author":[{"given":"Lauren V.","family":"Carruthers","sequence":"first","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C.","family":"Munday","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godwin U.","family":"Ebiloma","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow Glasgow UK"},{"name":"School of Health and Life Sciences Teesside University Middlesbrough UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Steketee","sequence":"additional","affiliation":[{"name":"Roslin Institute Royal (Dick) School of Veterinary Sciences University of Edinburgh Edinburgh 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