{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:16:51Z","timestamp":1767827811789,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0005641","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T00:00:00Z","timestamp":1497398400000}}],"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T00:00:00Z","timestamp":1496361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kaladrug-R","award":["EC-FP7-222895"],"award-info":[{"award-number":["EC-FP7-222895"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0005641","type":"journal-article","created":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T17:38:42Z","timestamp":1496425122000},"page":"e0005641","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":73,"title":["Increased miltefosine tolerance in clinical isolates of Leishmania donovani is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress"],"prefix":"10.1371","volume":"11","author":[{"given":"Deepak Kumar","family":"Deep","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruchi","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasundhra","family":"Bhandari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditya","family":"Verma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanila","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saima","family":"Wajid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyam","family":"Sundar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Ramesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Claude","family":"Dujardin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-4872","authenticated-orcid":true,"given":"Poonam","family":"Salotra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2017,6,2]]},"reference":[{"key":"ref1","unstructured":"WHO (2010) Report of a meeting of the WHO expert committee on the control of Leishmaniases, Geneva, 22\u201326 March, 2010."},{"key":"ref2","doi-asserted-by":"crossref","first-page":"e832","DOI":"10.1371\/journal.pntd.0000832","article-title":"Enhance case detection and improved diagnosis of PKDL in a Kala-azar-endemic area of Bangladesh","volume":"4","author":"D Mondal","year":"2010","journal-title":"Plos Negl Trop Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"e0004289","DOI":"10.1371\/journal.pntd.0004289","article-title":"Decline in clinical efficacy of oral miltefosine in treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) in India","volume":"9","author":"V Ramesh","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1056\/NEJMoa021556","article-title":"Oral miltefosine for Indian visceral leishmaniasis","volume":"347","author":"S Sundar","year":"2002","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/cid\/cis474","article-title":"Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use","volume":"55","author":"S Sundar","year":"2012","journal-title":"Clin Infect Dis"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1093\/cid\/cit102","article-title":"Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance","volume":"56","author":"S Rijal","year":"2013","journal-title":"Clin Infect Dis"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"e1657","DOI":"10.1371\/journal.pntd.0001657","article-title":"Drug susceptibility in <italic>Leishmania<\/italic> isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis","volume":"6","author":"V Bhandari","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"ref8","first-page":"e00611","article-title":"Relapse after treatment with miltefosine for visceral leishmaniasis is associated with increased infectivity of the infecting <italic>Leishmania donovani<\/italic> strain","volume":"4","author":"K Rai","year":"2013","journal-title":"MBio"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1086\/505079","article-title":"Visceral leishmaniasis, or kala azar (KA): high incidence of refractoriness to antimony is contributed by anthroponotic transmission via post-KA dermal leishmaniasis","volume":"194","author":"R Singh","year":"2006","journal-title":"J Infect Dis"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1128\/AAC.47.8.2397-2403.2003","article-title":"<italic>Leishmania donovani<\/italic> resistance to miltefosine involves a defective inward translocation of the drug","volume":"47","author":"FJ Perez-Victoria","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S0924-8579(03)00125-0","article-title":"Characterisation of <italic>Leishmania donovani<\/italic> promastigotes resistant to hexadecylphosphocholine (miltefosine)","volume":"22","author":"K Seifert","year":"2003","journal-title":"Int J Antimicrob Agents"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s00436-014-3755-6","article-title":"Comparative transcript expression analysis of miltefosine-sensitive and miltefosine-resistant <italic>Leishmania donovani<\/italic>","volume":"113","author":"A Kulshrestha","year":"2014","journal-title":"Parasitol Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"23766","DOI":"10.1074\/jbc.M605214200","article-title":"Phospholipid translocation and miltefosine potency require both <italic>L<\/italic>. <italic>donovani<\/italic> miltefosine transporter and the new protein LdRos3 in <italic>Leishmania<\/italic> parasites","volume":"281","author":"FJ Perez-Victoria","year":"2006","journal-title":"J Biol Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1111\/febs.12449","article-title":"Miltefosine-unresponsive <italic>Leishmania donovani<\/italic> has a greater ability than miltefosine-responsive <italic>L<\/italic>. <italic>donovani<\/italic> to resist reactive oxygen species","volume":"280","author":"M Das","year":"2013","journal-title":"FEBS J"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.exppara.2013.08.004","article-title":"Miltefosine resistance in <italic>Leishmania donovani<\/italic> involve suppression of oxidative stress-induced programmed cell death","volume":"135","author":"J Mishra","year":"2013","journal-title":"Exp Parasitol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00436-012-3212-3","article-title":"Validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of <italic>Leishmania donovani<\/italic>","volume":"112","author":"A Kulshrestha","year":"2013","journal-title":"Parasitol Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.ijpara.2011.07.013","article-title":"Characterisation of antimony-resistant <italic>Leishmania donovan<\/italic>i isolates: biochemical and biophysical studies and interaction with host cells","volume":"41","author":"R Mukhopadhyay","year":"2011","journal-title":"Int. J. Parasitol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ijantimicag.2010.03.012","article-title":"Overexpression of histone H2A modulates drug susceptibility in <italic>Leishmania<\/italic> parasites","volume":"36","author":"R Singh","year":"2010","journal-title":"Int J Antimicrob Agents"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1128\/AAC.00812-10","article-title":"Antimony resistant clinical isolates of <italic>Leishmania donovani<\/italic> are susceptible to paromomycin and sitamaquine","volume":"55","author":"A Kulshrestha","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"564","DOI":"10.4049\/jimmunol.135.1.564","article-title":"Identification of cell surface carbohydrate and antigenic changes between noninfective and infective developmental stages of <italic>Leishmania major<\/italic> promastigotes","volume":"135","author":"DL Sacks","year":"1985","journal-title":"J Immunol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1186\/s12864-016-2672-8","article-title":"<italic>In vitro<\/italic> infectivity and differential gene expression of <italic>Leishmania infantum<\/italic> metacyclic promastigotes: negative selection with peanut agglutinin in culture versus isolation from the stomodeal valve of <italic>Phlebotomus perniciosus<\/italic>","volume":"17","author":"PJ Alcolea","year":"2016","journal-title":"BMC Genomics"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jchromb.2008.02.005","article-title":"Development and validation of a quantitative assay for the measurement of miltefosine in human plasma by liquid chromatography-tandem mass spectrometry","volume":"865","author":"TP Dorlo","year":"2008","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1051\/parasite\/1998052167","article-title":"Development and characterization of paromomycin-resistant <italic>Leishmania donovani<\/italic> promastigotes","volume":"5","author":"M Maarouf","year":"1998","journal-title":"Parasite"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1128\/AAC.50.5.1788-1797.2006","article-title":"Sodium antimony gluconate induces generation of reactive oxygen species and nitric oxide via phosphoinositide 3-kinase and mitogen-activated protein kinase activation in <italic>Leishmania donovani<\/italic>-infected macrophages","volume":"50","author":"J Mookerjee Basu","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2011.09.030","article-title":"Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations","volume":"52","author":"B Kalyanaraman","year":"2012","journal-title":"Free Radic Biol Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e85715","DOI":"10.1371\/journal.pone.0085715","article-title":"Infection with <italic>Leishmania major<\/italic> induces a cellular stress response in macrophages","volume":"9","author":"AA Filardy","year":"2014","journal-title":"PLoS One"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1128\/AAC.50.1.88-95.2006","article-title":"Resistance to <italic>Leishmania donovani<\/italic> to sodium stibogluconate is related to the expression of host and parasite gamma-glutamylcysteine synthetase","volume":"50","author":"KC Carter","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00436-012-2823-z","article-title":"Biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of <italic>Leishmania donovani<\/italic>","volume":"111","author":"D Kumar","year":"2012","journal-title":"Parasitol Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e1469","DOI":"10.1371\/journal.pntd.0001469","article-title":"Impact of continuous axenic cultivation in <italic>Leishmania infantum<\/italic> virulence","volume":"6","author":"D Moreira","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"ref30","first-page":"305","article-title":"Low plasma membrane expression of the miltefosine transport complex renders <italic>Leishmania braziliensis<\/italic> refractory to the drug","volume":"53","author":"MP Sanchez-Ca\u00f1ete","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e0154101","DOI":"10.1371\/journal.pone.0154101","article-title":"Genomic and molecular characterization of miltefosine resistance in <italic>Leishmania infantum<\/italic> strains with either natural or acquired resistance through experimental selection of intracellular amastigotes","volume":"11","author":"A Mondelaers","year":"2016","journal-title":"PLoS One"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1128\/AAC.48.3.852-859.2004","article-title":"Miltefosine induces apoptosis-like death in <italic>Leishmania donovani<\/italic> promastigotes","volume":"48","author":"C Paris","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.48.8.3010-3015.2004","article-title":"Possible mechanism of miltefosine-mediated death of <italic>Leishmania donovani<\/italic>","volume":"48","author":"NK Verma","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1096\/fj.14-258624","article-title":"Metabolic reconfiguration of the central glucose metabolism: a crucial strategy of <italic>Leishmania donovani<\/italic> for its survival during oxidative stress","volume":"29","author":"AK Ghosh","year":"2015","journal-title":"FASEB J"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s11010-010-0433-6","article-title":"Identification, characterization and expression of a unique secretory lipase from the human pathogen <italic>Leishmania donovani<\/italic>","volume":"341","author":"AM Shakarian","year":"2010","journal-title":"Mol Cell Biochem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s00216-014-7772-1","article-title":"Multi-analytical platform metabolomic approach to study miltefosine mechanism of action and resistance in <italic>Leishmania<\/italic>","volume":"406","author":"GA Canuto","year":"2014","journal-title":"Anal Bioanal Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1128\/AAC.00478-16","article-title":"Genomic appraisal of the multifactorial basis for <italic>in vitro<\/italic> acquisition of miltefosine resistance in <italic>Leishmania donovani<\/italic>","volume":"60","author":"P Vacchina","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1186\/s13071-016-1904-8","article-title":"A mitochondrial HSP70 (HSPA9B) is linked to miltefosine resistance and stress response in <italic>Leishmania donovani<\/italic>","volume":"9","author":"P Vacchina","year":"2016","journal-title":"Parasit Vectors"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0005641","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T00:00:00Z","timestamp":1497398400000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0005641","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T14:54:25Z","timestamp":1719240865000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0005641"}},"subtitle":[],"editor":[{"given":"Mitali","family":"Chatterjee","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,6,2]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0005641","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0005641","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,2]]}}}