{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T12:13:54Z","timestamp":1767183234560,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011112","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000}}],"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R15AI156746"],"award-info":[{"award-number":["R15AI156746"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI139198"],"award-info":[{"award-number":["R01AI139198"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P41-GM103422"],"award-info":[{"award-number":["P41-GM103422"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P60-DK20579"],"award-info":[{"award-number":["P60-DK20579"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P30-DK56341"],"award-info":[{"award-number":["P30-DK56341"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Biomedical Mass Spectrometry Resource at Washington University in St. Louis"},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Glycerophospholipids including phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are vital components of biological membranes. Trypanosomatid parasites of the genus\n                    <jats:italic>Leishmania<\/jats:italic>\n                    can acquire PE and PC via\n                    <jats:italic>de novo<\/jats:italic>\n                    synthesis and the uptake\/remodeling of host lipids. In this study, we investigated the ethanolaminephosphate cytidylyltransferase (EPCT) in\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    , which is the causative agent for cutaneous leishmaniasis. EPCT is a key enzyme in the ethanolamine branch of the Kennedy pathway which is responsible for the\n                    <jats:italic>de novo<\/jats:italic>\n                    synthesis of PE. Our results demonstrate that\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>major<\/jats:italic>\n                    EPCT is a cytosolic protein capable of catalyzing the formation of CDP-ethanolamine from ethanolamine-phosphate and cytidine triphosphate. Genetic manipulation experiments indicate that EPCT is essential in both the promastigote and amastigote stages of\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>major<\/jats:italic>\n                    as the chromosomal null mutants cannot survive without the episomal expression of EPCT. This differs from our previous findings on the choline branch of the Kennedy pathway (responsible for PC synthesis) which is required only in promastigotes but not amastigotes. While episomal EPCT expression does not affect promastigote proliferation under normal conditions, it leads to reduced production of ethanolamine plasmalogen or plasmenylethanolamine, the dominant PE subtype in\n                    <jats:italic>Leishmania<\/jats:italic>\n                    . In addition, parasites with episomal EPCT exhibit heightened sensitivity to acidic pH and starvation stress, and significant reduction in virulence. In summary, our investigation demonstrates that proper regulation of EPCT expression is crucial for PE synthesis, stress response, and survival of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    parasites throughout their life cycle.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011112","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T13:35:57Z","timestamp":1690551357000},"page":"e1011112","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major"],"prefix":"10.1371","volume":"19","author":[{"given":"Somrita","family":"Basu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattie C.","family":"Pawlowic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fong-Fu","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoff","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6616-1806","authenticated-orcid":true,"given":"Kai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"issue":"5","key":"ppat.1011112.ref001","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"},{"issue":"10009","key":"ppat.1011112.ref002","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1016\/S0140-6736(15)61340-X","article-title":"Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990\u20132013: quantifying the epidemiological transition","volume":"386","author":"GBD DALYs","year":"2015","journal-title":"Lancet"},{"issue":"1","key":"ppat.1011112.ref003","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":"4","key":"ppat.1011112.ref004","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1017\/S0031182016002523","article-title":"Chemotherapy of leishmaniasis: present challenges","volume":"145","author":"SRB Uliana","year":"2018","journal-title":"Parasitology"},{"issue":"1","key":"ppat.1011112.ref005","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/0005-2760(94)90186-4","article-title":"Phosphatidylcholine breakdown and signal transduction","volume":"1212","author":"JH Exton","year":"1994","journal-title":"Biochimica et biophysica acta"},{"issue":"4","key":"ppat.1011112.ref006","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3109\/09687688.2015.1066894","article-title":"Phosphatidylcholine\u2019s functions beyond that of a membrane brick","volume":"32","author":"S Furse","year":"2015","journal-title":"Mol Membr Biol"},{"issue":"5","key":"ppat.1011112.ref007","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1002\/j.1460-2075.1993.tb05839.x","article-title":"Phosphatidylethanolamine is the donor of the terminal phosphoethanolamine group in trypanosome glycosylphosphatidylinositols","volume":"12","author":"AK Menon","year":"1993","journal-title":"EMBO J"},{"issue":"16","key":"ppat.1011112.ref008","doi-asserted-by":"crossref","first-page":"11384","DOI":"10.1074\/jbc.M512307200","article-title":"Endosome sorting and autophagy are essential for differentiation and virulence of Leishmania major","volume":"281","author":"S Besteiro","year":"2006","journal-title":"The Journal of biological chemistry"},{"issue":"5","key":"ppat.1011112.ref009","doi-asserted-by":"crossref","first-page":"e1002695","DOI":"10.1371\/journal.ppat.1002695","article-title":"ATG5 is essential for ATG8-dependent autophagy and mitochondrial homeostasis in Leishmania major","volume":"8","author":"RA Williams","year":"2012","journal-title":"PLoS pathogens"},{"issue":"29","key":"ppat.1011112.ref010","doi-asserted-by":"crossref","first-page":"20320","DOI":"10.1074\/jbc.M802430200","article-title":"Phosphatidylethanolamine is the precursor of the ethanolamine phosphoglycerol moiety bound to eukaryotic elongation factor 1A","volume":"283","author":"A Signorell","year":"2008","journal-title":"The Journal of biological chemistry"},{"issue":"1","key":"ppat.1011112.ref011","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0021-9258(19)50784-0","article-title":"The synthesis of cytidine diphosphate choline, cytidine diphosphate ethanolamine, and related compounds","volume":"222","author":"EP Kennedy","year":"1956","journal-title":"The Journal of biological chemistry"},{"issue":"4","key":"ppat.1011112.ref012","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/sj.emboj.7601565","article-title":"Redirection of sphingolipid metabolism toward de novo synthesis of ethanolamine in Leishmania","volume":"26","author":"K Zhang","year":"2007","journal-title":"EMBO J"},{"issue":"22","key":"ppat.1011112.ref013","doi-asserted-by":"crossref","first-page":"8585","DOI":"10.1016\/S0021-9258(19)40710-2","article-title":"Ethanolaminephosphate cytidylyltransferase. Purification and characterization of the enzyme from rat liver","volume":"250","author":"R. Sundler","year":"1975","journal-title":"The Journal of biological chemistry"},{"issue":"2","key":"ppat.1011112.ref014","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/mmi.13387","article-title":"Plasmenylethanolamine synthesis in Leishmania major","volume":"101","author":"MC Pawlowic","year":"2016","journal-title":"Molecular microbiology"},{"issue":"3","key":"ppat.1011112.ref015","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1194\/jlr.M200426-JLR200","article-title":"Separate myocardial ethanolamine phosphotransferase activities responsible for plasmenylethanolamine and phosphatidylethanolamine synthesis","volume":"44","author":"DA Ford","year":"2003","journal-title":"Journal of lipid research"},{"issue":"35","key":"ppat.1011112.ref016","doi-asserted-by":"crossref","first-page":"23636","DOI":"10.1074\/jbc.M803600200","article-title":"Phosphatidylethanolamine in Trypanosoma brucei is organized in two separate pools and is synthesized exclusively by the Kennedy pathway","volume":"283","author":"A Signorell","year":"2008","journal-title":"The Journal of biological chemistry"},{"issue":"2","key":"ppat.1011112.ref017","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1042\/bj3390291","article-title":"Cloning and expression of a human choline\/ethanolaminephosphotransferase: synthesis of phosphatidylcholine and phosphatidylethanolamine","volume":"339","author":"AL Henneberry","year":"1999","journal-title":"The Biochemical journal"},{"key":"ppat.1011112.ref018","doi-asserted-by":"crossref","first-page":"647870","DOI":"10.3389\/fcimb.2021.647870","article-title":"De Novo Synthesis of Phosphatidylcholine Is Essential for the Promastigote But Not Amastigote Stage in Leishmania major","volume":"11","author":"S Moitra","year":"2021","journal-title":"Frontiers in cellular and infection microbiology"},{"issue":"7","key":"ppat.1011112.ref019","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1194\/jlr.R700020-JLR200","article-title":"Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids","volume":"49","author":"JE Vance","year":"2008","journal-title":"Journal of lipid research"},{"issue":"6","key":"ppat.1011112.ref020","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1016\/j.bbamem.2013.10.018","article-title":"Phospholipid methylation in mammals: from biochemistry to physiological function","volume":"1838","author":"DE Vance","year":"2014","journal-title":"Biochimica et biophysica acta"},{"issue":"2","key":"ppat.1011112.ref021","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.molbiopara.2014.08.005","article-title":"Characterization of Leishmania major phosphatidylethanolamine methyltransferases LmjPEM1 and LmjPEM2 and their inhibition by choline analogs","volume":"196","author":"SS Bibis","year":"2014","journal-title":"Molecular and biochemical parasitology"},{"issue":"2","key":"ppat.1011112.ref022","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0005-2736(03)00131-7","article-title":"The overexpression of a new ABC transporter in Leishmania is related to phospholipid trafficking and reduced infectivity","volume":"1612","author":"A Parodi-Talice","year":"2003","journal-title":"Biochimica et biophysica acta"},{"issue":"5","key":"ppat.1011112.ref023","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/j.1365-2958.2007.05653.x","article-title":"A novel ATP-binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl-phospholipids","volume":"64","author":"E Castanys-Munoz","year":"2007","journal-title":"Molecular microbiology"},{"key":"ppat.1011112.ref024","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.mib.2021.07.004","article-title":"Balancing de novo synthesis and salvage of lipids by Leishmania amastigotes","volume":"63","author":"K. Zhang","year":"2021","journal-title":"Current opinion in microbiology"},{"issue":"2","key":"ppat.1011112.ref025","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molbiopara.2009.12.004","article-title":"Phospholipid and sphingolipid metabolism in Leishmania","volume":"170","author":"K Zhang","year":"2010","journal-title":"Molecular and biochemical parasitology"},{"key":"ppat.1011112.ref026","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/978-1-0716-1410-5_14","article-title":"Shotgun Lipidomic Analysis of Leishmania Cells","volume":"2306","author":"K Zhang","year":"2021","journal-title":"Methods Mol Biol"},{"issue":"10","key":"ppat.1011112.ref027","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0020-7519(03)00142-5","article-title":"Two separate growth phases during the development of Leishmania in sand flies: implications for understanding the life cycle","volume":"33","author":"SM Gossage","year":"2003","journal-title":"International journal for parasitology"},{"issue":"7","key":"ppat.1011112.ref028","doi-asserted-by":"crossref","first-page":"e1003672","DOI":"10.1371\/journal.pgen.1003672","article-title":"The mating competence of geographically diverse Leishmania major strains in their natural and unnatural sand fly vectors","volume":"9","author":"E Inbar","year":"2013","journal-title":"PLoS genetics"},{"issue":"1","key":"ppat.1011112.ref029","doi-asserted-by":"crossref","first-page":"e1003888","DOI":"10.1371\/journal.ppat.1003888","article-title":"Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism","volume":"10","author":"EC Saunders","year":"2014","journal-title":"PLoS pathogens"},{"issue":"5","key":"ppat.1011112.ref030","first-page":"E801","article-title":"Continual renewal and replication of persistent Leishmania major parasites in concomitantly immune hosts","volume":"114","author":"MA Mandell","year":"2017","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"11","key":"ppat.1011112.ref031","doi-asserted-by":"crossref","first-page":"102522","DOI":"10.1016\/j.jbc.2022.102522","article-title":"Inositol phosphorylceramide synthase null Leishmania are viable and virulent in animal infections where salvage of host sphingomyelin predominates","volume":"298","author":"FM Kuhlmann","year":"2022","journal-title":"The Journal of biological chemistry"},{"issue":"5","key":"ppat.1011112.ref032","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1111\/j.1365-2958.2005.04493.x","article-title":"Leishmania salvage and remodelling of host sphingolipids in amastigote survival and acidocalcisome biogenesis","volume":"55","author":"K Zhang","year":"2005","journal-title":"Molecular microbiology"},{"issue":"10","key":"ppat.1011112.ref033","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 pathogens"},{"issue":"8","key":"ppat.1011112.ref034","doi-asserted-by":"crossref","first-page":"e1008810","DOI":"10.1371\/journal.ppat.1008810","article-title":"Sterol 14-alpha-demethylase is vital for mitochondrial functions and stress tolerance in Leishmania major","volume":"16","author":"S Mukherjee","year":"2020","journal-title":"PLoS pathogens"},{"key":"ppat.1011112.ref035","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/0076-6879(92)09032-X","article-title":"Ethanolamine-phosphate cytidylyltransferase","volume":"209","author":"LB Tijburg","year":"1992","journal-title":"Methods Enzymol"},{"issue":"2","key":"ppat.1011112.ref036","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.3390\/ijms14022529","article-title":"Regulation of Phosphatidylethanolamine Homeostasis&#8212;The Critical Role of CTP:Phosphoethanolamine Cytidylyltransferase (Pcyt2)","volume":"14","author":"Z Pavlovic","year":"2013","journal-title":"Int J Mol Sci"},{"issue":"9","key":"ppat.1011112.ref037","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1128\/MCB.01527-06","article-title":"Developmental and metabolic effects of disruption of the mouse CTP:phosphoethanolamine cytidylyltransferase gene (Pcyt2)","volume":"27","author":"MD Fullerton","year":"2007","journal-title":"Mol Cell Biol"},{"issue":"38","key":"ppat.1011112.ref038","doi-asserted-by":"crossref","first-page":"25704","DOI":"10.1074\/jbc.M109.023846","article-title":"The development of a metabolic disease phenotype in CTP:phosphoethanolamine cytidylyltransferase-deficient mice","volume":"284","author":"MD Fullerton","year":"2009","journal-title":"The Journal of biological chemistry"},{"issue":"40","key":"ppat.1011112.ref039","doi-asserted-by":"crossref","first-page":"27077","DOI":"10.1074\/jbc.M109.031336","article-title":"Elimination of the CDP-ethanolamine pathway disrupts hepatic lipid homeostasis","volume":"284","author":"R Leonardi","year":"2009","journal-title":"The Journal of biological chemistry"},{"issue":"4","key":"ppat.1011112.ref040","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1111\/j.1365-2958.2009.06713.x","article-title":"Perturbation of phosphatidylethanolamine synthesis affects mitochondrial morphology and cell-cycle progression in procyclic-form Trypanosoma brucei","volume":"72","author":"A Signorell","year":"2009","journal-title":"Molecular microbiology"},{"issue":"5","key":"ppat.1011112.ref041","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1111\/j.1365-2958.2009.06764.x","article-title":"The ethanolamine branch of the Kennedy pathway is essential in the bloodstream form of Trypanosoma brucei","volume":"73","author":"F Gibellini","year":"2009","journal-title":"Molecular microbiology"},{"issue":"1","key":"ppat.1011112.ref042","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0166-6851(96)02580-7","article-title":"Use of the green fluorescent protein as a marker in transfected Leishmania","volume":"77","author":"DS Ha","year":"1996","journal-title":"Molecular and biochemical parasitology"},{"issue":"2","key":"ppat.1011112.ref043","first-page":"231","article-title":"Heat-shock protein 83 of Leishmania mexicana amazonensis is an abundant cytoplasmic protein with a tandemly repeated genomic arrangement. European journal of biochemistry \/","volume":"185","author":"M Shapira","year":"1989","journal-title":"FEBS"},{"key":"ppat.1011112.ref044","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1146\/annurev.mi.46.100192.000433","article-title":"The lipophosphoglycan of Leishmania parasites","volume":"46","author":"SJ Turco","year":"1992","journal-title":"Annual review of microbiology"},{"issue":"1","key":"ppat.1011112.ref045","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrg980","article-title":"Protozomics: trypanosomatid parasite genetics comes of age","volume":"4","author":"SM Beverley","year":"2003","journal-title":"Nat Rev Genet"},{"issue":"6","key":"ppat.1011112.ref046","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1111\/j.1365-2958.2009.06610.x","article-title":"Methylene tetrahydrofolate dehydrogenase\/cyclohydrolase and the synthesis of 10-CHO-THF are essential in Leishmania major","volume":"71","author":"SM Murta","year":"2009","journal-title":"Molecular microbiology"},{"issue":"3","key":"ppat.1011112.ref047","doi-asserted-by":"crossref","first-page":"e0003588","DOI":"10.1371\/journal.pntd.0003588","article-title":"Targeting Ergosterol biosynthesis in Leishmania donovani: essentiality of sterol 14 alpha-demethylase","volume":"9","author":"LI McCall","year":"2015","journal-title":"PLoS neglected tropical diseases"},{"key":"ppat.1011112.ref048","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molbiopara.2019.03.001","article-title":"Farnesyl pyrophosphate synthase is essential for the promastigote and amastigote stages in Leishmania major","volume":"230","author":"S Mukherjee","year":"2019","journal-title":"Molecular and biochemical parasitology"},{"issue":"1","key":"ppat.1011112.ref049","doi-asserted-by":"crossref","first-page":"7602","DOI":"10.1038\/s41598-019-44086-6","article-title":"Phosphatidylcholine synthesis through cholinephosphate cytidylyltransferase is dispensable in Leishmania major","volume":"9","author":"S Moitra","year":"2019","journal-title":"Scientific reports"},{"key":"ppat.1011112.ref050","doi-asserted-by":"crossref","first-page":"709258","DOI":"10.3389\/fcimb.2021.709258","article-title":"Leishmania Exosomes\/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes","volume":"11","author":"Filho A da Silva Lira","year":"2021","journal-title":"Frontiers in cellular and infection microbiology"},{"issue":"22","key":"ppat.1011112.ref051","doi-asserted-by":"crossref","first-page":"15415","DOI":"10.1016\/S0021-9258(17)40693-4","article-title":"Ultrastructural localization of CTP:phosphoethanolamine cytidylyltransferase in rat liver","volume":"269","author":"JJ van Hellemond","year":"1994","journal-title":"The Journal of biological chemistry"},{"issue":"2","key":"ppat.1011112.ref052","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1039\/D0CB00171F","article-title":"Substrate inhibition by the blockage of product release and its control by tunnel engineering","volume":"2","author":"P Kokkonen","year":"2021","journal-title":"RSC Chem Biol"},{"key":"ppat.1011112.ref053","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3389\/fcimb.2012.00072","article-title":"Impact of Leishmania metalloprotease GP63 on macrophage signaling","volume":"2","author":"A Isnard","year":"2012","journal-title":"Frontiers in cellular and infection microbiology"},{"issue":"10","key":"ppat.1011112.ref054","doi-asserted-by":"crossref","first-page":"e1010640","DOI":"10.1371\/journal.ppat.1010640","article-title":"Revisiting Leishmania GP63 host cell targets reveals a limited spectrum of substrates","volume":"18","author":"MM Guay-Vincent","year":"2022","journal-title":"PLoS pathogens"},{"issue":"5","key":"ppat.1011112.ref055","doi-asserted-by":"crossref","first-page":"e1005658","DOI":"10.1371\/journal.ppat.1005658","article-title":"Cysteine Peptidase B Regulates Leishmania mexicana Virulence through the Modulation of GP63 Expression","volume":"12","author":"PA Casgrain","year":"2016","journal-title":"PLoS pathogens."},{"issue":"6","key":"ppat.1011112.ref056","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.4049\/jimmunol.155.6.3102","article-title":"Role of the Leishmania surface protease gp63 in complement fixation, cell adhesion, and resistance to complement-mediated lysis","volume":"155","author":"A Brittingham","year":"1995","journal-title":"J Immunol"},{"issue":"13","key":"ppat.1011112.ref057","doi-asserted-by":"crossref","first-page":"9570","DOI":"10.1016\/S0021-9258(18)98389-4","article-title":"Inhibition of glycosylphosphatidylinositol biosynthesis in Leishmania mexicana by mannosamine","volume":"268","author":"MC Field","year":"1993","journal-title":"The Journal of biological chemistry"},{"issue":"3\u20134","key":"ppat.1011112.ref058","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ijpara.2017.09.006","article-title":"Cyclopropane fatty acid synthesis affects cell shape and acid resistance in Leishmania mexicana","volume":"48","author":"W Xu","year":"2018","journal-title":"International journal for parasitology"},{"issue":"3","key":"ppat.1011112.ref059","first-page":"1084","article-title":"Stable transfection of the human parasite Leishmania major delineates a 30-kilobase region sufficient for extrachromosomal replication and expression","volume":"10","author":"GM Kapler","year":"1990","journal-title":"Mol Cell Biol"},{"issue":"18","key":"ppat.1011112.ref060","doi-asserted-by":"crossref","first-page":"7583","DOI":"10.1073\/pnas.0901698106","article-title":"Regulated expression of the Leishmania major surface virulence factor lipophosphoglycan using conditionally destabilized fusion proteins","volume":"106","author":"L Madeira da Silva","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"25","key":"ppat.1011112.ref061","doi-asserted-by":"crossref","first-page":"22703","DOI":"10.1074\/jbc.M302419200","article-title":"Properties of phosphoenolpyruvate mutase, the first enzyme in the aminoethylphosphonate biosynthetic pathway in Trypanosoma cruzi","volume":"278","author":"M Sarkar","year":"2003","journal-title":"The Journal of biological chemistry"},{"issue":"3","key":"ppat.1011112.ref062","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1017\/S0031182000056304","article-title":"Monoclonal antibodies to Leishmania tropica major: specificities and antigen location","volume":"85","author":"AA de Ibarra","year":"1982","journal-title":"Parasitology"},{"issue":"5","key":"ppat.1011112.ref063","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 Immunol"},{"issue":"4","key":"ppat.1011112.ref064","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"issue":"8","key":"ppat.1011112.ref065","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/o59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"EG Bligh","year":"1959","journal-title":"Canadian journal of biochemistry and physiology"},{"issue":"25","key":"ppat.1011112.ref066","doi-asserted-by":"crossref","first-page":"6387","DOI":"10.1007\/s00216-018-1252-y","article-title":"Mass spectrometry-based shotgun lipidomics\u2014a critical review from the technical point of view","volume":"410","author":"FF Hsu","year":"2018","journal-title":"Analytical and bioanalytical chemistry"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011112","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T13:41:14Z","timestamp":1691588474000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011112"}},"subtitle":[],"editor":[{"given":"Michael","family":"Boshart","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,28]]},"references-count":66,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011112","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,28]]}}}