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MIL\u2010R was easily induced in both strains using the promastigote\u2010stage, but a significant increase in MIL\u2010R in the intracellular amastigote compared to the corresponding wild\u2010type did not occur until promastigotes had adapted to 12.2 \u03bcM MIL. A variety of common and strain\u2010specific genetic changes were discovered in MIL\u2010adapted parasites, including deletions at the LdMT transporter gene, single\u2010base mutations and changes in somy. The most obvious lipid changes in MIL\u2010R promastigotes occurred to phosphatidylcholines and lysophosphatidylcholines and results indicate that the Kennedy pathway is involved in MIL resistance. The inherent Sb resistance of the parasite had an impact on the changes that occurred in MIL\u2010R parasites, with more genetic changes occurring in Sb\u2010R compared with Sb\u2010S parasites. Initial interpretation of the changes identified in this study does not support synergies with Sb\u2010R in the mechanisms of MIL resistance, though this requires an enhanced understanding of the parasite's biochemical pathways and how they are genetically regulated to be verified fully.<\/jats:p>","DOI":"10.1111\/mmi.13291","type":"journal-article","created":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T23:17:26Z","timestamp":1451431046000},"page":"1134-1148","source":"Crossref","is-referenced-by-count":75,"title":["<i>In vitro<\/i> selection of miltefosine resistance in promastigotes of <i>Leishmania donovani<\/i> from Nepal: genomic and metabolomic characterization"],"prefix":"10.1111","volume":"99","author":[{"given":"C. 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