{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:05:45Z","timestamp":1792037145045,"version":"4.4.0"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T00:00:00Z","timestamp":1438300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0003948","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T18:10:20Z","timestamp":1438366220000},"page":"e0003948","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":31,"title":["Fitness and Phenotypic Characterization of Miltefosine-Resistant Leishmania major"],"prefix":"10.1371","volume":"9","author":[{"given":"Kimbra G.","family":"Turner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Vacchina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maricela","family":"Robles-Murguia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariha","family":"Wadsworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Ann","family":"McDowell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,7,31]]},"reference":[{"issue":"9185","key":"ref1","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S0140-6736(98)10178-2","article-title":"Leishmaniasis","volume":"354","author":"BL Herwaldt","year":"1999","journal-title":"Lancet"},{"issue":"5","key":"ref2","doi-asserted-by":"crossref","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"J Alvar","year":"2012","journal-title":"PloS one"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1146\/annurev.mi.48.100194.002313","article-title":"The role of pH and temperature in the development of Leishmania parasites","volume":"48","author":"D Zilberstein","year":"1994","journal-title":"Annual review of microbiology"},{"issue":"6","key":"ref4","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S1995-7645(12)60084-4","article-title":"Leishmaniasis: current status of available drugs and new potential drug targets","volume":"5","author":"N Singh","year":"2012","journal-title":"Asian Pac J Trop Med"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1128\/CMR.19.1.111-126.2006","article-title":"Drug resistance in leishmaniasis","volume":"19","author":"SL Croft","year":"2006","journal-title":"Clinical microbiology reviews"},{"issue":"11","key":"ref6","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1093\/jac\/dks275","article-title":"Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis","volume":"67","author":"TP Dorlo","year":"2012","journal-title":"The Journal of antimicrobial chemotherapy"},{"issue":"4","key":"ref7","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1128\/AAC.01415-06","article-title":"Miltefosine (hexadecylphosphocholine) inhibits cytochrome c oxidase in Leishmania donovani promastigotes","volume":"51","author":"JR Luque-Ortega","year":"2007","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"14","key":"ref8","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1007\/s00216-014-7772-1","article-title":"Multi-analytical platform metabolomic approach to study miltefosine mechanism of action and resistance in Leishmania","volume":"406","author":"GA Canuto","year":"2014","journal-title":"Analytical and bioanalytical chemistry"},{"issue":"4","key":"ref9","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1590\/S0074-02762011000400021","article-title":"Miltefosine induces programmed cell death in Leishmania amazonensis promastigotes","volume":"106","author":"FD Marinho","year":"2011","journal-title":"Memorias do Instituto Oswaldo Cruz"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ijpddr.2013.11.002","article-title":"Untargeted metabolomic analysis of miltefosine action in Leishmania infantum reveals changes to the internal lipid metabolism","volume":"4","author":"IM Vincent","year":"2014","journal-title":"Int J Parasitol-Drug"},{"issue":"1\u20132","key":"ref11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.drup.2006.04.001","article-title":"Mechanisms of experimental resistance of Leishmania to miltefosine: Implications for clinical use","volume":"9","author":"FJ Perez-Victoria","year":"2006","journal-title":"Drug Resist Updat"},{"issue":"50","key":"ref12","doi-asserted-by":"crossref","first-page":"49965","DOI":"10.1074\/jbc.M308352200","article-title":"Functional cloning of the miltefosine transporter. A novel P-type phospholipid translocase from Leishmania involved in drug resistance","volume":"278","author":"FJ Perez-Victoria","year":"2003","journal-title":"The Journal of biological chemistry"},{"issue":"33","key":"ref13","doi-asserted-by":"crossref","first-page":"23766","DOI":"10.1074\/jbc.M605214200","article-title":"Phospholipid translocation and miltefosine potency require both L. donovani miltefosine transporter and the new protein LdRos3 in Leishmania parasites","volume":"281","author":"FJ Perez-Victoria","year":"2006","journal-title":"The Journal of biological chemistry"},{"issue":"5","key":"ref14","doi-asserted-by":"crossref","first-page":"e1657","DOI":"10.1371\/journal.pntd.0001657","article-title":"Drug susceptibility in Leishmania 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 neglected tropical diseases"},{"issue":"2","key":"ref15","doi-asserted-by":"crossref","first-page":"e1512","DOI":"10.1371\/journal.pntd.0001512","article-title":"Multiple mutations in heterogeneous miltefosine-resistant Leishmania major population as determined by whole genome sequencing","volume":"6","author":"AC Coelho","year":"2012","journal-title":"PLoS neglected tropical diseases"},{"issue":"4","key":"ref16","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3201\/eid1804.110841","article-title":"Leishmania resistance to miltefosine associated with genetic marker","volume":"18","author":"S Cojean","year":"2012","journal-title":"Emerg Infect Dis"},{"issue":"5","key":"ref17","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1007\/s00436-014-3835-7","article-title":"Experimental selection of paromomycin and miltefosine resistance in intracellular amastigotes of Leishmania donovani and L. infantum","volume":"113","author":"S Hendrickx","year":"2014","journal-title":"Parasitology research"},{"issue":"1","key":"ref18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/1574-6976.12032","article-title":"Drug resistance in vectorborne parasites: multiple actors and scenarios for an evolutionary arms race","volume":"38","author":"M Vanaerschot","year":"2014","journal-title":"FEMS microbiology reviews"},{"issue":"4","key":"ref19","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3109\/1040841X.2012.716818","article-title":"Drug-resistant microorganisms with a higher fitness\u2014can medicines boost pathogens?","volume":"39","author":"M Vanaerschot","year":"2013","journal-title":"Crit Rev Microbiol"},{"issue":"6","key":"ref20","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.ijantimicag.2007.01.004","article-title":"Leishmania spp.: proficiency of drug-resistant parasites","volume":"29","author":"S Natera","year":"2007","journal-title":"International journal of antimicrobial agents"},{"issue":"4","key":"ref21","doi-asserted-by":"crossref","first-page":"e0003704","DOI":"10.1371\/journal.pntd.0003704","article-title":"Fitness of Leishmania donovani Parasites Resistant to Drug Combinations","volume":"9","author":"R Garcia-Hernandez","year":"2015","journal-title":"PLoS neglected tropical diseases"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0091-679X(08)61846-4","article-title":"Transfection experiments with Leishmania","volume":"45","author":"JH LeBowitz","year":"1994","journal-title":"Methods Cell Biol"},{"issue":"3","key":"ref23","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1128\/AAC.02224-13","article-title":"In vitro screening test using Leishmania promastigotes stably expressing mCherry protein","volume":"58","author":"P Vacchina","year":"2014","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"21","key":"ref24","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"MA Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"ref25","doi-asserted-by":"crossref","DOI":"10.1002\/0471142727.mb1508s73","article-title":"High-throughput real-time quantitative reverse transcription PCR","author":"AL Bookout","year":"2006","journal-title":"Curr Protoc Mol Biol"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1128\/EC.00196-09","article-title":"Leishmania major MPK7 protein kinase activity inhibits intracellular growth of the pathogenic amastigote stage","volume":"9","author":"MA Morales","year":"2010","journal-title":"Eukaryotic cell"},{"issue":"6","key":"ref27","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1111\/j.1365-2583.2005.00601.x","article-title":"Characterization of a blood activated chitinolytic system in the midgut of the sand fly vectors Lutzomyia longipalpis and Phlebotomus papatasi","volume":"14","author":"JM Ramalho-Ortigao","year":"2005","journal-title":"Insect Mol Biol"},{"issue":"5","key":"ref28","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1365-3024.1985.tb00098.x","article-title":"A limiting dilution assay for quantifying Leishmania major in tissues of infected mice","volume":"7","author":"RG Titus","year":"1985","journal-title":"Parasite immunology"},{"issue":"Suppl 1","key":"ref29","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1016\/j.trstmh.2006.03.010","article-title":"Mechanisms of action of lysophospholipid analogues against trypanosomatid parasites","volume":"100","author":"JA Urbina","year":"2006","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"5","key":"ref30","doi-asserted-by":"crossref","first-page":"e1664","DOI":"10.1371\/journal.pntd.0001664","article-title":"Experimental induction of paromomycin resistance in antimony-resistant strains of L. donovani: outcome dependent on in vitro selection protocol","volume":"6","author":"S Hendrickx","year":"2012","journal-title":"PLoS neglected tropical diseases"},{"issue":"8","key":"ref31","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1128\/AAC.47.8.2397-2403.2003","article-title":"Leishmania donovani resistance to miltefosine involves a defective inward translocation of the drug","volume":"47","author":"FJ Perez-Victoria","year":"2003","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"4","key":"ref32","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1093\/jac\/dkq542","article-title":"In vitro interactions between sitamaquine and amphotericin B, sodium stibogluconate, miltefosine, paromomycin and pentamidine against Leishmania donovani","volume":"66","author":"K Seifert","year":"2011","journal-title":"The Journal of antimicrobial chemotherapy"},{"issue":"12","key":"ref33","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S1473-3099(05)70296-6","article-title":"Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India, 1980\u20132004","volume":"5","author":"PL Olliaro","year":"2005","journal-title":"The Lancet infectious diseases"},{"issue":"11","key":"ref34","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1128\/IAI.55.11.2802-2806.1987","article-title":"Metacyclogenesis is a major determinant of Leishmania promastigote virulence and attenuation","volume":"55","author":"R da Silva","year":"1987","journal-title":"Infection and immunity"},{"issue":"Pt 2","key":"ref35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1042\/bj3560335","article-title":"Characterization of a differentially expressed protein that shows an unusual localization to intracellular membranes in Leishmania major","volume":"356","author":"E Knuepfer","year":"2001","journal-title":"The Biochemical journal"},{"issue":"11","key":"ref36","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1017\/S0031182011001120","article-title":"Increased metacyclogenesis of antimony-resistant Leishmania donovani clinical lines","volume":"138","author":"M Ouakad","year":"2011","journal-title":"Parasitology"},{"issue":"Pt 6","key":"ref37","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1017\/S0031182004005098","article-title":"Cell differentiation and infectivity of Leishmania mexicana are inhibited in a strain resistant to an ABC-transporter blocker","volume":"128","author":"N Silva","year":"2004","journal-title":"Parasitology"},{"issue":"9","key":"ref38","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1128\/AAC.41.9.1898","article-title":"In vitro life cycle of pentamidine-resistant amastigotes: stability of the chemoresistant phenotypes is dependent on the level of resistance induced","volume":"41","author":"D Sereno","year":"1997","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"1","key":"ref39","doi-asserted-by":"crossref","first-page":"e2646","DOI":"10.1371\/journal.pntd.0002646","article-title":"LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major","volume":"8","author":"B Norris-Mullins","year":"2014","journal-title":"PLoS neglected tropical diseases"},{"issue":"1","key":"ref40","doi-asserted-by":"crossref","first-page":"e1469","DOI":"10.1371\/journal.pntd.0001469","article-title":"Impact of continuous axenic cultivation in Leishmania infantum virulence","volume":"6","author":"D Moreira","year":"2012","journal-title":"PLoS neglected tropical diseases"},{"issue":"8","key":"ref41","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1128\/AAC.49.8.3274-3280.2005","article-title":"Production and characterization of stable amphotericin-resistant amastigotes and promastigotes of Leishmania mexicana","volume":"49","author":"HI Al-Mohammed","year":"2005","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"8","key":"ref42","doi-asserted-by":"crossref","first-page":"e23120","DOI":"10.1371\/journal.pone.0023120","article-title":"Antimonial resistance in Leishmania donovani is associated with increased in vivo parasite burden","volume":"6","author":"M Vanaerschot","year":"2011","journal-title":"PloS one"},{"issue":"8","key":"ref43","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.pt.2008.05.004","article-title":"Fitness costs of resistance to antimalarial drugs","volume":"24","author":"I Felger","year":"2008","journal-title":"Trends in parasitology"},{"issue":"4","key":"ref44","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S0924-8579(03)00125-0","article-title":"Characterisation of Leishmania donovani promastigotes resistant to hexadecylphosphocholine (miltefosine)","volume":"22","author":"K Seifert","year":"2003","journal-title":"International journal of antimicrobial agents"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0003948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,6]],"date-time":"2020-09-06T19:07:04Z","timestamp":1599419224000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0003948"}},"subtitle":[],"editor":[{"given":"Louis","family":"Maes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,7,31]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2015,7,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0003948","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,31]]}}}