{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:22:57Z","timestamp":1790997777681,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010779","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000}}],"reference-count":174,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100002425","name":"Governo Brasil","doi-asserted-by":"publisher","award":["201535\/2015-7"],"award-info":[{"award-number":["201535\/2015-7"]}],"id":[{"id":"10.13039\/501100002425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007145","name":"Fakulti Perubatan dan Sains Kesihatan, Universiti Putra Malaysia","doi-asserted-by":"publisher","award":["KPT (BS) 850101016636"],"award-info":[{"award-number":["KPT (BS) 850101016636"]}],"id":[{"id":"10.13039\/501100007145","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC Confidence in Concept","award":["MRC Confidence in Concept MC-PC-17157"],"award-info":[{"award-number":["MRC Confidence in Concept MC-PC-17157"]}]},{"DOI":"10.13039\/100016270","name":"Global Challenges Research Fund","doi-asserted-by":"publisher","award":["MR\/P027989\/1"],"award-info":[{"award-number":["MR\/P027989\/1"]}],"id":[{"id":"10.13039\/100016270","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC Newton grant","award":["MRC Newton grant MR\/S019650\/1 -\"Bridging epigenetics, metabolism and cell cycle in pathogenic trypanosomatids\")"],"award-info":[{"award-number":["MRC Newton grant MR\/S019650\/1 -\"Bridging epigenetics, metabolism and cell cycle in pathogenic trypanosomatids\")"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Wellcome Centre for Molecular Parasitology 104111\/Z\/14\/Z"],"award-info":[{"award-number":["Wellcome Centre for Molecular Parasitology 104111\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Amphotericin B is increasingly used in treatment of leishmaniasis. Here, fourteen independent lines of\n                    <jats:italic>Leishmania mexicana<\/jats:italic>\n                    and one\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>infantum<\/jats:italic>\n                    line were selected for resistance to either amphotericin B or the related polyene antimicrobial, nystatin. Sterol profiling revealed that, in each resistant line, the predominant wild-type sterol, ergosta-5,7,24-trienol, was replaced by other sterol intermediates. Broadly, two different profiles emerged among the resistant lines. Whole genome sequencing then showed that these distinct profiles were due either to mutations in the sterol methyl transferase (C24SMT) gene locus or the sterol C5 desaturase (C5DS) gene. In three lines an additional deletion of the miltefosine transporter gene was found. Differences in sensitivity to amphotericin B were apparent, depending on whether cells were grown in HOMEM, supplemented with foetal bovine serum, or a serum free defined medium (DM). Metabolomic analysis after exposure to AmB showed that a large increase in glucose flux via the pentose phosphate pathway preceded cell death in cells sustained in HOMEM but not DM, indicating the oxidative stress was more significantly induced under HOMEM conditions. Several of the lines were tested for their ability to infect macrophages and replicate as amastigote forms, alongside their ability to establish infections in mice. While several AmB resistant lines showed reduced virulence, at least two lines displayed heightened virulence in mice whilst retaining their resistance phenotype, emphasising the risks of resistance emerging to this critical drug.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0010779","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T14:12:31Z","timestamp":1664374351000},"page":"e0010779","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":52,"title":["Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-6365","authenticated-orcid":true,"given":"Edubiel A.","family":"Alpizar-Sosa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Raihana Binti","family":"Ithnin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Pountain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan K.","family":"Weidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Donachie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Ritchie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A.","family":"Dickie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J. S.","family":"Burchmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Denny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-3519","authenticated-orcid":true,"given":"Michael P.","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"issue":"10151","key":"pntd.0010779.ref001","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"S Burza","year":"2018","journal-title":"Lancet"},{"issue":"3","key":"pntd.0010779.ref002","doi-asserted-by":"crossref","first-page":"100207","DOI":"10.4172\/2157-7625.1000207","article-title":"Sandfly and Leishmaniasis: A Review","volume":"6","author":"M Ghazanfar","year":"2016","journal-title":"J Ecosys Ecograp"},{"issue":"3","key":"pntd.0010779.ref003","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S1473-3099(16)30217-1","article-title":"Global burden of cutaneous leishmaniasis","volume":"17","author":"C Karimkhani","year":"2017","journal-title":"Lancet Infect Dis"},{"issue":"3","key":"pntd.0010779.ref004","first-page":"1","article-title":"To evaluate efficacy and safety of amphotericin B in two different doses in the treatment of Post kala-azar dermal leishmaniasis (PKDL)","volume":"12","author":"VNR Das","year":"2017","journal-title":"PLoS ONE"},{"issue":"1","key":"pntd.0010779.ref005","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev-med-051214-024241","article-title":"New Vaccines for the World\u2019s Poorest People","volume":"67","author":"PJ Hotez","year":"2016","journal-title":"Annu Rev Med"},{"issue":"5","key":"pntd.0010779.ref006","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1128\/AAC.40.5.1214","article-title":"Therapy of visceral leishmaniasis due to Leishmania infantum: experimental assessment of efficacy of AmBisome","volume":"40","author":"JP Gangneux","year":"1996","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"pntd.0010779.ref007","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1128\/AAC.44.9.2327-2332.2000","article-title":"Single-dose AmBisome (liposomal amphotericin B) as prophylaxis for murine systemic candidiasis and histoplasmosis","volume":"44","author":"A Garcia","year":"2000","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pntd.0010779.ref008","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/bmb\/lds031","article-title":"Management of trypanosomiasis and leishmaniasis","volume":"104","author":"MP Barrett","year":"2012","journal-title":"Br Med Bull"},{"issue":"1","key":"pntd.0010779.ref009","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.drudis.2017.09.006","article-title":"Molecular targets and pathways for the treatment of visceral leishmaniasis","volume":"23","author":"V Jain","year":"2018","journal-title":"Drug Discov Tod"},{"issue":"12","key":"pntd.0010779.ref010","doi-asserted-by":"crossref","first-page":"e0006052","DOI":"10.1371\/journal.pntd.0006052","article-title":"Drug resistance and treatment failure in leishmaniasis: A 21st century challenge","volume":"11","author":"A Ponte-Sucre","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010779.ref011","first-page":"397","volume-title":"Mechanisms of drug resistance volume","author":"S McCarthy MM","year":"2017"},{"issue":"4","key":"pntd.0010779.ref012","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1128\/AAC.41.4.752","article-title":"Activity of liposomal amphotericin B against experimental cutaneous leishmaniasis","volume":"41","author":"V Yardley","year":"1997","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"pntd.0010779.ref013","doi-asserted-by":"crossref","first-page":"16092","DOI":"10.1038\/nmicrobiol.2016.92","article-title":"Drug resistance in eukaryotic microorganisms","volume":"20161","author":"AH Fairlamb","journal-title":"Nature Microbiol"},{"issue":"29","key":"pntd.0010779.ref014","doi-asserted-by":"crossref","first-page":"7278","DOI":"10.1021\/jp020160s","article-title":"Revealing the orientation of nystatin and amphotericin B in lipidic multilayers by UV-Vis linear dichroism","volume":"106","author":"S Lopes","year":"2002","journal-title":"J Phys Chem B"},{"issue":"2","key":"pntd.0010779.ref015","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.bbamem.2018.11.006","article-title":"The pore-forming action of polyenes: From model membranes to living organisms","volume":"861","author":"L Kristanc","year":"2019","journal-title":"Biochim Biophys Acta\u2014Biomemb"},{"key":"pntd.0010779.ref016","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0304-4157(86)90002-X","article-title":"How do the polyene macrolide antibiotics affect the cellular membrane properties?","volume":"864","author":"J. Bolard","year":"1986","journal-title":"Biochim Biophys Acta"},{"issue":"1\u20132","key":"pntd.0010779.ref017","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.bbrc.2011.11.023","article-title":"A novel mechanism for an old drug: Amphotericin B in the treatment of visceral leishmaniasis","volume":"416","author":"A Chattopadhyay","year":"2011","journal-title":"Biochem Biophys Res Comm"},{"issue":"9","key":"pntd.0010779.ref018","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nrd3074","article-title":"An insight into the antifungal pipeline: Selected new molecules and beyond","volume":"9","author":"L Ostrosky-Zeichner","year":"2010","journal-title":"Nature Rev Drug Discov"},{"key":"pntd.0010779.ref019","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/713687","article-title":"Antifungal resistance and new strategies to control fungal infections","volume":"2012","author":"P Vandeputte","year":"2012","journal-title":"Int J Microbiol"},{"issue":"3","key":"pntd.0010779.ref020","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nrmicro1835","article-title":"The evolution of fungal drug resistance: Modulating the trajectory from genotype to phenotype","volume":"6","author":"LE Cowen","year":"2008","journal-title":"Nature Rev Microbiol"},{"issue":"9","key":"pntd.0010779.ref021","doi-asserted-by":"crossref","first-page":"5122","DOI":"10.1128\/AAC.00878-16","article-title":"The role of signaling via aqueous pore formation in resistance responses to Amphotericin B","volume":"60","author":"BE Cohen","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"pntd.0010779.ref022","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1093\/jac\/dkl005","article-title":"Comparative study on the efficacy of amBisome and fungizone in a mouse model of pulmonary aspergillosis","volume":"57","author":"K Takemoto","year":"2006","journal-title":"J Antimicrob Chemother"},{"issue":"4","key":"pntd.0010779.ref023","doi-asserted-by":"crossref","first-page":"566","DOI":"10.4269\/ajtmh.2011.10-0662","article-title":"Case report: Central nervous system toxicity associated with liposomal amphotericin B therapy for cutaneous leishmaniasis","volume":"84","author":"JS Glasser","year":"2011","journal-title":"Am J Trop Med Hyg"},{"issue":"4","key":"pntd.0010779.ref024","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1177\/0049475514543655","article-title":"Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome) infusion","volume":"44","author":"P Nath","year":"2014","journal-title":"Tropical Doctor"},{"issue":"1","key":"pntd.0010779.ref025","first-page":"25","article-title":"Efficacy and safety of liposomal amphotericin B (AmBisome) for visceral leishmaniasis in endemic developing countries","volume":"76","author":"JD Berman","year":"1998","journal-title":"1998; Bull World Health Organ"},{"issue":"9764","key":"pntd.0010779.ref026","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0140-6736(10)62050-8","article-title":"Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial","volume":"377","author":"S Sundar","year":"2011","journal-title":"Lancet"},{"issue":"10","key":"pntd.0010779.ref027","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1111\/j.1469-0691.2011.03635.x","article-title":"Leishmaniasis impact and treatment access","volume":"17","author":"M den Boer","year":"2011","journal-title":"Clin Microbiol Infect"},{"issue":"3","key":"pntd.0010779.ref028","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1007\/s12639-014-0607-3","article-title":"Treatment of visceral leishmaniasis: anomalous pricing and distribution of AmBisome and emergence of an indigenous liposomal amphotericin B, FUNGISOME","volume":"40","author":"P Bhattacharya","year":"2016","journal-title":"J Parasit Dis"},{"issue":"4","key":"pntd.0010779.ref029","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1517\/14728214.2012.748036","article-title":"Liposomal amphotericin B as a treatment for human leishmaniasis","volume":"17","author":"M Balasegaram","year":"2012","journal-title":"Exp Opin Emerg Drugs"},{"issue":"4","key":"pntd.0010779.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/CMR.00048-18","article-title":"Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives","volume":"31","author":"F Alves","year":"2018","journal-title":"Clin Microbiol Rev"},{"key":"pntd.0010779.ref031","author":"WHO","year":"2013","journal-title":"Department of Control of Neglected Tropical Diseases Sustaining the drive to overcome the global impact of neglected tropical diseases Second WHO report on neglected tropical diseases"},{"key":"pntd.0010779.ref032","author":"MSF","year":"2011","journal-title":"MSF statement in response to Gilead donation of AmBisome for visceral leishmaniasis | M\u00e9decins Sans Fronti\u00e8res Access Campaign"},{"issue":"8749","key":"pntd.0010779.ref033","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/0140-6736(91)91708-3","article-title":"Liposomal amphotericin B in drug-resistant visceral leishmaniasis","volume":"337","author":"RN Davidson","year":"1991","journal-title":"Lancet"},{"issue":"2","key":"pntd.0010779.ref034","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/tropej\/fmp073","article-title":"Successful treatment of childhood cutaneous leishmaniasis with liposomal amphotericin B: Report of two cases","volume":"56","author":"T del Rosal","year":"2009","journal-title":"J Trop Pediat"},{"issue":"1","key":"pntd.0010779.ref035","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1590\/S0037-86822008000100018","article-title":"Mucocutaneous leishmaniasis treated with liposomal amphotericin B","volume":"41","author":"JR Lambertucci","year":"2008","journal-title":"Rev Soc Bras Med Trop"},{"issue":"4","key":"pntd.0010779.ref036","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0924-8579(99)00133-8","article-title":"A comparison of the activities of three amphotericin B lipid formulations against experimental visceral and cutaneous leishmaniasis","volume":"13","author":"V Yardley","year":"2000","journal-title":"Int J Antimicrob Agent"},{"issue":"26","key":"pntd.0010779.ref037","first-page":"267","article-title":"Kala-azar in India\u2013progress and challenges towards its elimination as a public health problem","author":"N Gill","year":"2021","journal-title":"Weekly Epidem Rec"},{"key":"pntd.0010779.ref038","doi-asserted-by":"crossref","first-page":"k5224","DOI":"10.1136\/bmj.k5224","article-title":"Eliminating visceral leishmaniasis in South Asia: The road ahead","volume":"364","author":"S Rijal","year":"2019","journal-title":"BMJ"},{"issue":"35","key":"pntd.0010779.ref039","first-page":"401","article-title":"Global leishmaniasis surveillance: 2019\u20132020, a baseline for the 2030 roadmap","volume":"96","author":"JA Ruiz-Postigo","year":"2021","journal-title":"Wkly Epidemiol Rec"},{"key":"pntd.0010779.ref040","volume-title":"Ending the neglect to attain the Sustainable Development Goals\u2013A road map for neglected tropical diseases 2021\u20132030","author":"WHO","year":"2020"},{"key":"pntd.0010779.ref041","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/trstmh\/trab002","article-title":"A road map for neglected tropical diseases 2021\u20132030","volume":"115","author":"MN Malecela","year":"2021","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"supsl. S1","key":"pntd.0010779.ref042","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/jac\/49.suppl_1.7","article-title":"Amphotericin B: Spectrum and resistance","volume":"49","author":"D. Ellis","year":"2002","journal-title":"J Antimicrob Chemother"},{"key":"pntd.0010779.ref043","first-page":"1","article-title":"It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug","volume":"3","author":"AC Mesa-Arango","year":"2012","journal-title":"Front Microbiol"},{"issue":"5","key":"pntd.0010779.ref044","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.micinf.2011.01.015","article-title":"Amphotericin B mediates killing in Cryptococcus neoformans through the induction of a strong oxidative burst","volume":"13","author":"F Sangalli-Leite","year":"2011","journal-title":"Microbes Infect"},{"key":"pntd.0010779.ref045","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1093\/mmy\/myx119","article-title":"Aspergillus terreus: Novel lessons learned on amphotericin B resistance","volume":"56","author":"W Posch","year":"2018","journal-title":"Med Mycol"},{"issue":"1","key":"pntd.0010779.ref046","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/jac\/49.1.209","article-title":"Resistance to amphotericin B does not emerge during treatment for invasive aspergillosis","volume":"49","author":"M-YS Moosa","year":"2002","journal-title":"J Antimicrob Chemother"},{"issue":"2","key":"pntd.0010779.ref047","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1086\/595710","article-title":"Parasite susceptibility to Amphotericin B in failures of treatment for visceral leishmaniasis in patients coinfected with HIV type 1 and Leishmania infantum","volume":"48","author":"L Lachaud","year":"2009","journal-title":"Clin Infect Dis"},{"issue":"1","key":"pntd.0010779.ref048","doi-asserted-by":"crossref","first-page":"e2611","DOI":"10.1371\/journal.pntd.0002611","article-title":"Post Kala-Azar dermal leishmaniasis following treatment with 20 mg\/kg liposomal amphotericin B (Ambisome) for primary visceral leishmaniasis in Bihar, India","volume":"8","author":"S Burza","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"pntd.0010779.ref049","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/clinids\/12.2.308","article-title":"Amphotericin B: 30 years of clinical experience","volume":"12","author":"HA Gallis","year":"1990","journal-title":"Rev Infect Dis"},{"issue":"4","key":"pntd.0010779.ref050","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1085\/jgp.65.4.515","article-title":"Pores formed in lipid bilayer membranes by nystatin, differences in its one-sided and two-sided action","volume":"65","author":"A Marty","year":"1975","journal-title":"J Gen Physiol"},{"issue":"1","key":"pntd.0010779.ref051","first-page":"1","article-title":"The polyene antifungals, amphotericin B and nystatin, cause cell death in Saccharomyces cerevisiae by a distinct mechanism to amphibian-derived antimicrobial peptides","volume":"13","author":"G Serhan","year":"2014","journal-title":"Annal Clin Microbiol Antimicrob"},{"issue":"10","key":"pntd.0010779.ref052","doi-asserted-by":"crossref","first-page":"6393","DOI":"10.1074\/jbc.M707821200","article-title":"Natamycin blocks fungal growth by binding specifically to ergosterol without permeabilizing the membrane","volume":"283","author":"YM Te Welscher","year":"2008","journal-title":"J Biol Chem"},{"issue":"6","key":"pntd.0010779.ref053","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1128\/AAC.01794-09","article-title":"Natamycin inhibits vacuole fusion at the priming phase via a specific interaction with ergosterol","volume":"54","author":"YM Te Welscher","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"pntd.0010779.ref054","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.bbrc.2005.11.062","article-title":"The sterol-binding antibiotic nystatin inhibits entry of non-opsonized Leishmania donovani into macrophages","volume":"339","author":"P Tewary","year":"2006","journal-title":"Biochem Biophys Res Comm"},{"issue":"5","key":"pntd.0010779.ref055","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nchembio.1496","article-title":"Amphotericin forms an extramembranous and fungicidal sterol sponge","volume":"10","author":"TM Anderson","year":"2014","journal-title":"Nature Chem Biol"},{"issue":"3","key":"pntd.0010779.ref056","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1128\/AAC.4.3.309","article-title":"Selective membrane toxicity of the polyene antibiotics: studies on lecithin membrane models (liposomes)","volume":"4","author":"C-C Hsuchen","year":"1973","journal-title":"Antimicrob Agents Chemother"},{"issue":"10","key":"pntd.0010779.ref057","doi-asserted-by":"crossref","first-page":"5427","DOI":"10.1128\/MCB.16.10.5427","article-title":"Transcriptional regulation by ergosterol in the yeast Saccharomyces cerevisiae","volume":"16","author":"SJ Smith","year":"1996","journal-title":"Mol Cell Biol"},{"issue":"5","key":"pntd.0010779.ref058","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1042\/BST0331178","article-title":"Interactions of the ergosterol biosynthetic pathway with other lipid pathways","volume":"33","author":"M Veen","year":"2005","journal-title":"Biochem Soc Trans"},{"issue":"2","key":"pntd.0010779.ref059","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1128\/AAC.00030-11","article-title":"Mechanism of amphotericin B resistance in clinical isolates of Leishmania donovani","volume":"56","author":"B Purkait","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pntd.0010779.ref060","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/jac\/44.1.71","article-title":"Flow cytometric assessment of amphotericin B susceptibility in Leishmania infantum isolates from patients with visceral leishmaniasis","volume":"44","author":"C di Giorgio","year":"1999","journal-title":"J Antimicrob Chemother"},{"issue":"8","key":"pntd.0010779.ref061","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1128\/AAC.42.8.2141","article-title":"Leishmania infantum: Lack of parasite resistance to amphotericin B in a clinically resistant visceral leishmaniasis","volume":"42","author":"R Durand","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"issue":"8","key":"pntd.0010779.ref062","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1128\/JCM.00173-11","article-title":"Unusual case of resistance to amphotericin B in visceral leishmaniasis in a region in India where leishmaniasis is not endemic","volume":"49","author":"P Srivastava","year":"2011","journal-title":"J Clin Microbiol"},{"issue":"2","key":"pntd.0010779.ref063","doi-asserted-by":"crossref","first-page":"167","DOI":"10.4103\/0974-777X.62887","article-title":"Drug resistance in leishmaniasis","volume":"2","author":"J Chakravarty","year":"2010","journal-title":"J Global Infect Dis"},{"issue":"2","key":"pntd.0010779.ref064","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s00436-015-4793-4","article-title":"Cross-resistance of Leishmania infantum isolates to nitric oxide from patients refractory to antimony treatment, and greater tolerance to antileishmanial responses by macrophages","volume":"115","author":"TR de Moura","year":"2016","journal-title":"Parasitol Res"},{"issue":"1","key":"pntd.0010779.ref065","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12879-017-2192-4","article-title":"A severe case of visceral leishmaniasis and liposomal amphotericin B treatment failure in an immunosuppressed patient 15 years after exposure","volume":"17","author":"A Eichenberger","year":"2017","journal-title":"BMC Infect Dis"},{"issue":"1","key":"pntd.0010779.ref066","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1186\/s12879-016-1746-1","article-title":"Safety and efficacy of liposomal amphotericin B for treatment of complicated visceral leishmaniasis in patients without HIV, North-West Ethiopia","volume":"16","author":"A Tamiru","year":"2016","journal-title":"BMC Infect Dis"},{"issue":"12","key":"pntd.0010779.ref067","doi-asserted-by":"crossref","first-page":"e152","DOI":"10.1093\/cid\/cir674","article-title":"Limited effectiveness of high-dose liposomal amphotericin B (AmBisome) for treatment of visceral leishmaniasis in an Ethiopian population with high HIV prevalence","volume":"53","author":"K Ritmeijer","year":"2011","journal-title":"Clin Infect Dis"},{"key":"pntd.0010779.ref068","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.micpath.2018.09.014","article-title":"Candida auris: Epidemiology, risk factors, virulence, resistance, and therapeutic options","volume":"125","author":"CO Sardi de","year":"2018","journal-title":"Microb Pathogen"},{"issue":"8","key":"pntd.0010779.ref069","doi-asserted-by":"crossref","first-page":"575.e1","DOI":"10.1016\/j.cmi.2017.02.002","article-title":"Impact of ERG3 mutations and expression of ergosterol genes controlled by UPC2 and NDT80 in Candida parapsilosis azole resistance","volume":"23","author":"J Branco","year":"2017","journal-title":"Clin Microbiol Infect"},{"issue":"1\u20132","key":"pntd.0010779.ref070","first-page":"29","article-title":"Defective sterol \u03945(6)desaturase as a cause of azole resistance in Ustilago maydis","volume":"127","author":"T Joseph-Horne","year":"1995","journal-title":"FEMS Microbiol Lett"},{"issue":"1\u20132","key":"pntd.0010779.ref071","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1574-6968.1994.tb07140.x","article-title":"Resistance to amphotericin B associated with defective sterol \u03948,7, isomerase in a Cryptococcus neoformans strain from an AIDS patient","volume":"122","author":"SL Kelly","year":"1994","journal-title":"FEMS Microbiol Lett"},{"issue":"9","key":"pntd.0010779.ref072","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1128\/AAC.00303-10","article-title":"A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B","volume":"54","author":"CM Martel","journal-title":"Antimicrob Agents Chemother"},{"issue":"5","key":"pntd.0010779.ref073","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1093\/jac\/dkg434","article-title":"Treatment failure in invasive aspergillosis: Susceptibility of deep tissue isolates following treatment with amphotericin B","volume":"52","author":"PJ Paterson","year":"2003","journal-title":"J Antimicrob Chemother"},{"issue":"9","key":"pntd.0010779.ref074","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1128\/AAC.47.9.2717-2724.2003","article-title":"Disruption of ergosterol biosynthesis confers resistance to amphotericin B in Candida lusitaniae","volume":"47","author":"LY Young","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pntd.0010779.ref075","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/infdis\/154.1.76","article-title":"Amphotericin B-induced oxidative damage and killing of Candida albicans","volume":"154","author":"ML Sokol-Anderson","year":"1986","journal-title":"J Infect Dis"},{"issue":"10","key":"pntd.0010779.ref076","doi-asserted-by":"crossref","first-page":"e1001692","DOI":"10.1371\/journal.pbio.1001692","article-title":"Fitness Trade-offs Restrict the Evolution of Resistance to Amphotericin B","volume":"11","author":"BM Vincent","journal-title":"PLoS Biol."},{"key":"pntd.0010779.ref077","doi-asserted-by":"crossref","first-page":"103247","DOI":"10.1016\/j.fgb.2019.103247","article-title":"Antifungal resistance in Aspergillus terreus: A current scenario","volume":"131","author":"R Vahedi Shahandashti","year":"2019","journal-title":"Fungal Genet Biol"},{"key":"pntd.0010779.ref078","first-page":"1","article-title":"Genomic and Phenotypic Heterogeneity of Clinical Isolates of the Human Pathogens Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus fumigatiaffinis","volume":"11","author":"RAC dos Santos","year":"2020","journal-title":"Front. Genet"},{"issue":"3","key":"pntd.0010779.ref079","doi-asserted-by":"crossref","first-page":"536","DOI":"10.3201\/eid2303.160377","article-title":"Autochthonous outbreak and expansion of canine visceral Leishmaniasis, Uruguay","volume":"23","author":"D Satragno","year":"2017","journal-title":"Emerg Infect Dis"},{"issue":"8","key":"pntd.0010779.ref080","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1039\/D0MD00073F","article-title":"Leishmania infantum isolates exhibit high infectivity and reduced susceptibility to amphotericin B","volume":"11","author":"P Faral-Tello","year":"2020","journal-title":"RSC Med Chem"},{"issue":"4","key":"pntd.0010779.ref081","doi-asserted-by":"crossref","first-page":"e0196247","DOI":"10.1371\/journal.pone.0196247","article-title":"Intraspecies differences in natural susceptibility to amphotericine B of clinical isolates of Leishmania subgenus Viannia","volume":"13","author":"C Franco-Mu\u00f1oz","year":"2018","journal-title":"PLoS One"},{"issue":"5","key":"pntd.0010779.ref082","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1093\/jac\/dku534","article-title":"Up-regulation of silent information regulator 2 (Sir2) is associated with amphotericin B resistance in clinical isolates of Leishmania donovani","volume":"70","author":"B Purkait","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"pntd.0010779.ref083","first-page":"1","article-title":"Ergosterol biosynthesis in Aspergillus fumigatus: Its relevance as an antifungal target and role in antifungal drug resistance","volume":"3","author":"L Alcazar-Fuoli","year":"2012","journal-title":"Front Microbiol"},{"issue":"9312","key":"pntd.0010779.ref084","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/S0140-6736(02)08162-X","article-title":"Antifungal drug resistance of pathogenic fungi","volume":"359","author":"DP Kontoyiannis","year":"2002","journal-title":"Lancet"},{"key":"pntd.0010779.ref085","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/726328","article-title":"Comparative analysis of the omics technologies used to study antimonial, amphotericin B, and pentamidine resistance in Leishmania","volume":"2014","author":"G Kaur","year":"2014","journal-title":"J Parasitol Res"},{"issue":"2","key":"pntd.0010779.ref086","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ijpddr.2014.05.002","article-title":"Quantitative proteomic analysis of amphotericin B resistance in Leishmania infantum","volume":"4","author":"MC Brotherton","year":"2014","journal-title":"Int J Parasitol Drugs Drug Resist"},{"issue":"3","key":"pntd.0010779.ref087","first-page":"337","volume":"7","author":"J Singh","year":"2017","journal-title":"L-asparaginase of Leishmania donovani: Metabolic target and its role in Amphotericin B resistance Int J Parasitol Drugs Drug Resist"},{"key":"pntd.0010779.ref088","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.redox.2017.03.004","article-title":"Deciphering the interplay between cysteine synthase and thiol cascade proteins in modulating Amphotericin B resistance and survival of Leishmania donovani under oxidative stress","volume":"12","author":"K Singh","year":"2017","journal-title":"Redox Biol"},{"issue":"10","key":"pntd.0010779.ref089","doi-asserted-by":"crossref","first-page":"6172","DOI":"10.1128\/AAC.02834-14","article-title":"Ascorbate peroxidase, a key molecule regulating amphotericin B resistance in clinical isolates of Leishmania donovani","volume":"58","author":"A Kumar","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"pntd.0010779.ref090","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.biochi.2015.12.017","article-title":"Up-regulation of cytosolic tryparedoxin in Amp B resistant isolates of Leishmania donovani and its interaction with cytosolic tryparedoxin peroxidase","volume":"121","author":"SS Suman","year":"2016","journal-title":"Biochimie"},{"issue":"12","key":"pntd.0010779.ref091","doi-asserted-by":"crossref","first-page":"e0005171","DOI":"10.1371\/journal.pntd.0005171","article-title":"Different mutations in a P-type ATPase transporter in Leishmania parasites are associated with cross-resistance to two leading drugs by distinct mechanisms","volume":"10","author":"C Fernandez-Prada","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"pntd.0010779.ref092","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":"Int J Antimicrob Agents"},{"issue":"4","key":"pntd.0010779.ref093","doi-asserted-by":"crossref","first-page":"e0154101","DOI":"10.1371\/journal.pone.0154101","article-title":"Genomic and molecular characterization of miltefosine resistance in Leishmania infantum strains with either natural or acquired resistance through experimental selection of intracellular amastigotes","volume":"11","author":"A Mondelaers","year":"2016","journal-title":"PLoS One"},{"issue":"6","key":"pntd.0010779.ref094","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1111\/mmi.13291","article-title":"In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: Genomic and metabolomic characterization","volume":"99","author":"CD Shaw","year":"2016","journal-title":"Mol Microbiol"},{"issue":"6","key":"pntd.0010779.ref095","doi-asserted-by":"crossref","first-page":"e0005649","DOI":"10.1371\/journal.pntd.0005649","article-title":"Sterol 14\u03b1-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana","volume":"11","author":"R Mwenechanya","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"pntd.0010779.ref096","doi-asserted-by":"crossref","first-page":"e0007052","DOI":"10.1371\/journal.pntd.0007052","article-title":"Genomic instability at the locus of sterol C24-methyltransferase promotes amphotericin B resistance in Leishmania parasites","volume":"13","author":"AW Pountain","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"pntd.0010779.ref097","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1128\/AAC.42.2.352","volume":"42","author":"N Mbongo","year":"1998","journal-title":"Mechanism of Amphotericin B Resistance in Leishmania donovani promastigotes Antimicrob Agents Chemother"},{"issue":"7","key":"pntd.0010779.ref098","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1128\/AAC.48.7.2409-2414.2004","article-title":"Cloning of S-adenosyl-L-methionine:C-24-\u0394-sterol-methyltransferase (ERG6) from Leishmania donovani and characterization of mRNAs in wild-type and amphotericin B-resistant promastigotes","volume":"48","author":"M Pourshafie","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"pntd.0010779.ref099","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ijpddr.2018.04.002","article-title":"Genomic and transcriptomic alterations in Leishmania donovani lines experimentally resistant to antileishmanial drugs","volume":"8","author":"A Rastrojo","year":"2018","journal-title":"Int J Parasitol Drugs Drug Resist"},{"issue":"10","key":"pntd.0010779.ref100","doi-asserted-by":"crossref","first-page":"e1004427","DOI":"10.1371\/journal.ppat.1004427","article-title":"Sterol biosynthesis is required for heat resistance but not extracellular survival in Leishmania","volume":"10","author":"W Xu","year":"2014","journal-title":"PLoS Pathog"},{"issue":"3","key":"pntd.0010779.ref101","doi-asserted-by":"crossref","first-page":"e0003588","DOI":"10.1371\/journal.pntd.0003588","article-title":"Targeting ergosterol biosynthesis in Leishmania donovani: Essentiality of sterol 14alpha-demethylase","volume":"9","author":"LI McCall","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"8","key":"pntd.0010779.ref102","doi-asserted-by":"crossref","first-page":"e1008810","DOI":"10.1371\/journal.ppat.1008810","article-title":"Sterol 14-\u03b1-demethylase is vital for mitochondrial functions and stress tolerance in Leishmania major","volume":"16","author":"S Mukherjee","year":"2020","journal-title":"PLoS Pathog"},{"issue":"1","key":"pntd.0010779.ref103","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/mmi.14139","article-title":"Sterol methyltransferase is required for optimal mitochondrial function and virulence in Leishmania major","volume":"111","author":"S Mukherjee","year":"2019","journal-title":"Mol Microbiol"},{"issue":"4","key":"pntd.0010779.ref104","doi-asserted-by":"crossref","first-page":"e00380","DOI":"10.1128\/mSphere.00380-20","article-title":"Lathosterol oxidase (sterol C-5 desaturase) deletion confers resistance to amphotericin B and sensitivity to acidic stress in Leishmania major","volume":"5","author":"Y Ning","year":"2020","journal-title":"mSphere"},{"issue":"3","key":"pntd.0010779.ref105","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1128\/AAC.46.3.834-840.2002","article-title":"Plasma protein binding of amphotericin B and pharmacokinetics of bound versus unbound amphotericin B after administration of intravenous liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate","volume":"46","author":"I Bekersky","year":"2002","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"pntd.0010779.ref106","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1093\/infdis\/149.6.986","article-title":"Interaction of plasma proteins and lipoproteins with Amphotericin B","volume":"149","author":"J Brajtburg","year":"1984","journal-title":"J Infect Dis"},{"issue":"22","key":"pntd.0010779.ref107","doi-asserted-by":"crossref","first-page":"11242","DOI":"10.1021\/cr5003134","article-title":"Drug strategies targeting CYP51 in neglected tropical diseases","volume":"114","author":"JY Choi","year":"2014","journal-title":"Chem Rev"},{"key":"pntd.0010779.ref108","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ejmech.2017.04.044","article-title":"An overview of azoles targeting sterol 14\u03b1-demethylase for antileishmanial therapy","volume":"135","author":"S Emami","year":"2017","journal-title":"Eur J Med Chem"},{"issue":"12","key":"pntd.0010779.ref109","doi-asserted-by":"crossref","first-page":"e83247","DOI":"10.1371\/journal.pone.0083247","article-title":"In vitro activity of the antifungal azoles itraconazole and posaconazole against Leishmania amazonensis","volume":"8","author":"ST De Macedo-Silva","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"pntd.0010779.ref110","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1645\/GE-1259.1","article-title":"Mode of action of fenarimol Against Leishmania spp","volume":"94","author":"E Zeiman","year":"2008","journal-title":"Parasitol"},{"issue":"1","key":"pntd.0010779.ref111","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1021\/acsinfecdis.0c00546","article-title":"Antileishmanial chemotherapy through clemastine fumarate mediated inhibition of the Leishmania inositol phosphorylceramide synthase","volume":"7","author":"JGM Mina","year":"2021","journal-title":"ACS Infect Dis"},{"issue":"6","key":"pntd.0010779.ref112","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1039\/c0an00049c","article-title":"DNA interactions with a Methylene Blue redox indicator depend on the DNA length and are sequence specific","volume":"135","author":"E Farjami","year":"2010","journal-title":"Analyst"},{"issue":"28","key":"pntd.0010779.ref113","doi-asserted-by":"crossref","first-page":"15168","DOI":"10.1016\/S0021-9258(18)95717-0","article-title":"Methylene blue directly oxidizes glutathione without the intermediate formation of hydrogen peroxide","volume":"260","author":"MJ Kelner","year":"1985","journal-title":"J Biol Chem"},{"issue":"1","key":"pntd.0010779.ref114","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1128\/AAC.00773-07","article-title":"Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum","volume":"52","author":"K Buchholz","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"issue":"24","key":"pntd.0010779.ref115","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1093\/bioinformatics\/btx499","article-title":"PiMP my metabolome: an integrated, web-based tool for LC-MS metabolomics data","volume":"33","author":"Y Gloaguen","year":"2017","journal-title":"Bioinformatics"},{"issue":"5","key":"pntd.0010779.ref116","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1096\/fj.14-258624","article-title":"Metabolic reconfiguration of the central glucose metabolism: a crucial strategy of Leishmania donovani for its survival during oxidative stress","volume":"29","author":"A Ghosh","year":"2015","journal-title":"FASEB J"},{"issue":"3","key":"pntd.0010779.ref117","doi-asserted-by":"crossref","first-page":"e1006953","DOI":"10.1371\/journal.ppat.1006953","article-title":"Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana","volume":"14","author":"J Kov\u00e1\u0159ov\u00e1","year":"2018","journal-title":"PLoS Pathog"},{"issue":"1","key":"pntd.0010779.ref118","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1574-6968.2004.tb09522.x","article-title":"The pentose phosphate pathway in Trypanosoma cruzi","volume":"234","author":"DA Maugeri","year":"2004","journal-title":"FEMS Microbiol Lett"},{"issue":"7","key":"pntd.0010779.ref119","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1073\/pnas.1117280109","article-title":"Amphotericin primarily kills yeast by simply binding ergosterol","volume":"109","author":"KC Gray","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"pntd.0010779.ref120","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":"Antimicrob Agents Chemother"},{"key":"pntd.0010779.ref121","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s13071-016-1467-8","article-title":"Imipramine alters the sterol profile in Leishmania amazonensis and increases its sensitivity to miconazole","volume":"9","author":"VV Andrade-Neto","year":"2016","journal-title":"Parasit Vectors"},{"issue":"11","key":"pntd.0010779.ref122","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1128\/AAC.01545-16","article-title":"Antileishmanial activity of ezetimibe: Inhibition of sterol biosynthesis, in vitro synergy with azoles, and efficacy in experimental cutaneous leishmaniasis","volume":"60","author":"VV Andrade-Neto","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"pntd.0010779.ref123","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1093\/jac\/dkz515","article-title":"Stigmasterol as a potential biomarker for amphotericin B resistance in Leishmania donovani","volume":"75","author":"R Bansal","year":"2020","journal-title":"J Antimicrob Chemother"},{"issue":"4","key":"pntd.0010779.ref124","doi-asserted-by":"crossref","first-page":"e0007260","DOI":"10.1371\/journal.pntd.0007260","article-title":"A plant like cytochrome P450 subfamily CYP710C1 gene in Leishmania donovani encodes sterol C-22 desaturase and its over-expression leads to resistance to amphotericin B","volume":"13","author":"R Bansal","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"pntd.0010779.ref125","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0166-6851(02)00280-3","article-title":"Fatty acid and sterol metabolism: Potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa","volume":"126","author":"CW Roberts","year":"2003","journal-title":"Mol Biochem Parasitol"},{"key":"pntd.0010779.ref126","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/s13071-016-1470-0","article-title":"Dynamics of sterol synthesis during development of Leishmania spp. parasites to their virulent form","volume":"9","author":"C Yao","year":"2016","journal-title":"Parasit Vectors"},{"issue":"2\u20133","key":"pntd.0010779.ref127","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.actatropica.2011.05.001","article-title":"The pharmacological inhibition of sterol biosynthesis in Leishmania is counteracted by enhancement of LDL endocytosis","volume":"119","author":"VV Andrade-Neto","year":"2011","journal-title":"Acta Trop"},{"issue":"15","key":"pntd.0010779.ref128","doi-asserted-by":"crossref","first-page":"11674","DOI":"10.1074\/jbc.M006850200","article-title":"The biosynthetic incorporation of the intact leucine skeleton into sterol by the trypanosomatid Leishmania mexicana","volume":"276","author":"ML Ginger","year":"2001","journal-title":"J Biol Chem"},{"issue":"12","key":"pntd.0010779.ref129","doi-asserted-by":"crossref","first-page":"e3367","DOI":"10.1371\/journal.pntd.0003367","article-title":"Leishmania donovani infection enhances lateral mobility of macrophage membrane protein which is reversed by liposomal cholesterol","volume":"8","author":"M Ghosh","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"6","key":"pntd.0010779.ref130","doi-asserted-by":"crossref","first-page":"e97600","DOI":"10.1371\/journal.pone.0097600","article-title":"Stage-dependent expression and up-regulation of trypanothione synthetase in amphotericin B resistant Leishmania donovani","volume":"9","author":"A Equbal","year":"2014","journal-title":"PLoS One"},{"issue":"176","key":"pntd.0010779.ref131","first-page":"1","article-title":"Untargeted metabolomics to understand the basis of phenotypic differences in amphotericin B-resistant Leishmania parasites","volume":"4","author":"AW Pountain","year":"2019","journal-title":"Wellcome Open Res"},{"issue":"7","key":"pntd.0010779.ref132","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1128\/IAI.00214-13","article-title":"Attenuation of Leishmania infantum chagasi metacyclic promastigotes by sterol depletion","volume":"81","author":"C Yao","year":"2013","journal-title":"Infect Immun"},{"issue":"1","key":"pntd.0010779.ref133","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.exppara.2007.06.012","article-title":"Leishmania chagasi: Homogenous metacyclic promastigotes isolated by buoyant density are highly virulent in a mouse model","volume":"118","author":"C Yao","year":"2008","journal-title":"Exp Parasitol"},{"issue":"3","key":"pntd.0010779.ref134","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1046\/j.1365-2958.2000.01721.x","article-title":"Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress","volume":"35","author":"S Krieger","year":"2000","journal-title":"Mol Microbiol"},{"issue":"4","key":"pntd.0010779.ref135","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1590\/S0124-00642009000400015","article-title":"Evaluacion por Western Blot, [Western blot, ELISA and indirect immunofluorescence test evaluation of Leishmania (Leishmania) infantum-infected dogs]","volume":"11","author":"J Vargas","year":"2009","journal-title":"Rev Salud Publica (Bogota)"},{"issue":"1","key":"pntd.0010779.ref136","doi-asserted-by":"crossref","first-page":"e0006988","DOI":"10.1371\/journal.pntd.0006988","article-title":"A randomized trial of AmBisome monotherapy and AmBisome and miltefosine combination to treat visceral leishmaniasis in HIV co-infected patients in Ethiopia","volume":"13","author":"E Diro","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"pntd.0010779.ref137","doi-asserted-by":"crossref","first-page":"R115","DOI":"10.1186\/gb-2008-9-7-r115","article-title":"Modulation of gene expression in drug resistant Leishmania is associated with gene amplification, gene deletion and chromosome aneuploidy","volume":"9","author":"J-M Ubeda","year":"2008","journal-title":"Genome Biol"},{"issue":"1","key":"pntd.0010779.ref138","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1128\/AAC.44.1.63-67.2000","article-title":"The R467K amino acid substitution in Candida albicans sterol 14\u03b1- demethylase causes drug resistance through reduced affinity","volume":"44","author":"DC Lamb","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"pntd.0010779.ref139","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1128\/EC.00103-08","article-title":"A gain-of-function mutation in the transcription factor Upc2p causes upregulation of ergosterol biosynthesis genes and increased fluconazole resistance in a clinical Candida albicans isolate","volume":"7","author":"N Dunkel","year":"2008","journal-title":"Eukaryot Cell"},{"issue":"8","key":"pntd.0010779.ref140","doi-asserted-by":"crossref","first-page":"e00795","DOI":"10.1128\/AAC.00795-19","article-title":"Chemogenomic profiling of anti-leishmanial efficacy and resistance in the related kinetoplastid parasite Trypanosoma brucei","volume":"63","author":"CF Collett","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"issue":"5","key":"pntd.0010779.ref141","doi-asserted-by":"crossref","first-page":"e0009373","DOI":"10.1371\/journal.pntd.0009373","article-title":"New global targets for NTDs in the WHO roadmap 2021\u20132030","volume":"15","author":"A. Casulli","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"pntd.0010779.ref142","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1007\/s12639-021-01379-w","article-title":"Efficacy and safety of single-dose liposomal amphotericin B in patients with visceral leishmaniasis in Bangladesh: a real-life experience","volume":"45","author":"Amin MR Ekram MdR","year":"2021","journal-title":"J Parasit Dis"},{"issue":"3","key":"pntd.0010779.ref143","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.tmaid.2011.03.001","article-title":"Cutaneous leishmaniasis in three Dutch military cohorts following jungle training in Belize","volume":"9","author":"PP van Thiel","year":"2011","journal-title":"Travel Med Infect Dis"},{"issue":"1","key":"pntd.0010779.ref144","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2230.2004.01677.x","article-title":"Changing pattern of imported cutaneous leishmaniasis in the Netherlands","volume":"30","author":"JE Zeegelaar","year":"2005","journal-title":"Clin Exp Dermatol"},{"issue":"9","key":"pntd.0010779.ref145","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.3390\/pathogens10091112","article-title":"\"Chiclero\u2019s Ulcer\" Due to Leishmania mexicana in travelers returning from Central America: A case report and review of the literature","volume":"10","author":"C Eldin","year":"2021","journal-title":"Pathogens"},{"key":"pntd.0010779.ref146","volume-title":"Leishmaniasis in the Americas: Treatment recommendations","author":"Pan American Health Organization (PAHO)","year":"2018"},{"issue":"1","key":"pntd.0010779.ref147","doi-asserted-by":"crossref","first-page":"41","DOI":"10.4269\/ajtmh.1999.60.41","article-title":"Leishmania spp.: completely defined medium without serum and macromolecules (CDM\/LP) for the continuous in vitro cultivation of infective promastigote forms","volume":"60","author":"T Merlen","year":"1999","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0010779.ref148","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.exppara.2018.01.009","article-title":"A defined medium for Leishmania culture allows definition of essential amino acids","volume":"185","author":"A Nayak","year":"2018","journal-title":"Exp Parasitol"},{"issue":"4","key":"pntd.0010779.ref149","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1006\/expr.1993.1050","article-title":"Leishmania mexicana: Induction of Metacyclogenesis by cultivation of promastigotes at acidic pH","volume":"76","author":"PA Bates","year":"1993","journal-title":"Exp Parasitol"},{"issue":"9","key":"pntd.0010779.ref150","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.1128\/AAC.00548-09","article-title":"In vitro susceptibilities of Leishmania donovani promastigote and amastigote stages to antileishmanial reference drugs: Practical relevance of stage-specific differences","volume":"53","author":"M Vermeersch","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"issue":"Pt 2","key":"pntd.0010779.ref151","first-page":"193","article-title":"Axenic cultivation and characterization of Leishmania mexicana amastigote-like forms","volume":"105","author":"PA Bates","year":"1995","journal-title":"Parasitology"},{"issue":"2","key":"pntd.0010779.ref152","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.mimet.2008.05.026","article-title":"Rapid fluorescent assay for screening drugs on Leishmania amastigotes","volume":"75","author":"O Shimony","year":"2008","journal-title":"J Microbiol Methods"},{"issue":"3","key":"pntd.0010779.ref153","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S1383-5769(99)00020-3","article-title":"A simple colorimetric method to screen drug cytotoxicity against Leishmania using the dye Alamar Blue","volume":"48","author":"J Mikus","year":"2000","journal-title":"Parasitol Int"},{"issue":"1","key":"pntd.0010779.ref154","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/0014-4894(84)90022-5","article-title":"Leishmania mexicana: Serial cultivation of intracellular stages in a cell-free medium","volume":"58","author":"AA Pan","year":"1984","journal-title":"Exp Parasitol"},{"key":"pntd.0010779.ref155","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actatropica.2014.02.012","article-title":"Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and inhibits the polyamine transport in Trypanosoma cruzi","volume":"134","author":"M v D\u00edaz","year":"2014","journal-title":"Acta Trop"},{"issue":"5","key":"pntd.0010779.ref156","doi-asserted-by":"crossref","first-page":"e00450","DOI":"10.1128\/mSphere.00450-19","article-title":"Deletion of a single LeishIF4E-3 allele by the CRISPR-Cas9 system alters cell morphology and infectivity of Leishmania","volume":"4","author":"R Shrivastava","year":"2019","journal-title":"mSphere"},{"issue":"2","key":"pntd.0010779.ref157","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1093\/jac\/dkw409","article-title":"In vitro \u2018time-to-kill\u2019 assay to assess the cidal activity dynamics of current reference drugs against Leishmania donovani and Leishmania infantum","volume":"72","author":"L Maes","year":"2017","journal-title":"J Antimicrob Chemother"},{"issue":"3","key":"pntd.0010779.ref158","doi-asserted-by":"crossref","first-page":"421","DOI":"10.4269\/ajtmh.1998.59.421","article-title":"Transformation, development, and transmission of axenically cultured amastigotes of Leishmania mexicana in vitro and in Lutzomyia longipalpis","volume":"59","author":"AY Ismaeel","year":"1998","journal-title":"Am J Trop Med Hyg"},{"issue":"7","key":"pntd.0010779.ref159","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1021\/ac2000994","article-title":"PeakML\/mzMatch: A file format, Java library, R library, and tool-chain for mass spectrometry data analysis","volume":"83","author":"RA Scheltema","year":"2011","journal-title":"Anal Chem"},{"issue":"2","key":"pntd.0010779.ref160","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.molbiopara.2011.10.003","article-title":"Metabolomic analysis of trypanosomatid protozoa","volume":"181","author":"DJ Creek","year":"2012","journal-title":"Mol Biochem Parasitol"},{"issue":"7","key":"pntd.0010779.ref161","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1093\/bioinformatics\/bts069","article-title":"Burgess KE v., Breitling R, Barrett MP. IDEOM: an Excel interface for analysis of LC\u2013MS-based metabolomics data","volume":"28","author":"DJ Creek","year":"2012","journal-title":"Bioinformatics"},{"key":"pntd.0010779.ref162","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/978-1-0716-0239-3_21","article-title":"Using the IDEOM workflow for LCMS-based metabolomics studies of drug mechanisms","volume":"2104","author":"A. Srivastava","year":"2020","journal-title":"Methods Mol Biol"},{"issue":"D1","key":"pntd.0010779.ref163","first-page":"D440","article-title":"MetaboLights: A resource evolving in response to the needs of its scientific community","volume":"48","author":"K Haug","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"pntd.0010779.ref164","article-title":"Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM","author":"H. Li","year":"2013","journal-title":"arXiv:1303.3997v2 [Preprint]"},{"issue":"9","key":"pntd.0010779.ref165","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"A McKenna","year":"2010","journal-title":"Genome Res"},{"key":"pntd.0010779.ref166","article-title":"Calling somatic SNVs and indels with Mutect2","author":"D Benjamin","year":"2019","journal-title":"BioRxiv"},{"issue":"2","key":"pntd.0010779.ref167","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"P Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"issue":"1","key":"pntd.0010779.ref168","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative Genome Viewer","volume":"29","author":"JT Robinson","year":"2011","journal-title":"Nat Biotechnol"},{"issue":"22","key":"pntd.0010779.ref169","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","article-title":"CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice","volume":"22","author":"JD Thompson","year":"1994","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"pntd.0010779.ref170","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"D Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"pntd.0010779.ref171","doi-asserted-by":"crossref","first-page":"D561","DOI":"10.1093\/nar\/gkq973","article-title":"The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored","volume":"39","author":"D Szklarczyk","year":"2011","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"pntd.0010779.ref172","doi-asserted-by":"crossref","first-page":"D412","DOI":"10.1093\/nar\/gkn760","article-title":"STRING 8 \u2013A global view on proteins and their functional interactions in 630 organisms","volume":"37","author":"LJ Jensen","year":"2009","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"pntd.0010779.ref173","doi-asserted-by":"crossref","first-page":"D433","DOI":"10.1093\/nar\/gki005","article-title":"STRING: Known and predicted protein-protein associations, integrated and transferred across organisms","volume":"33","author":"C von Mering","year":"2005","journal-title":"Nucl Acids Res"},{"key":"pntd.0010779.ref174","doi-asserted-by":"crossref","first-page":"642502","DOI":"10.1155\/2009\/642502","article-title":"Sterol biosynthesis pathway as target for anti-trypanosomatid drugs","volume":"2009","author":"W de Souza","year":"2009","journal-title":"Interdiscip Perspect Infect Dis"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0010779","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010779","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T13:49:14Z","timestamp":1666187354000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010779"}},"subtitle":[],"editor":[{"given":"Mitali","family":"Chatterjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,9,28]]},"references-count":174,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0010779","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,28]]}}}