{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:43:41Z","timestamp":1791899021635,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012978","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000}}],"reference-count":76,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015592","name":"Canadian Institute for Military and Veteran Health Research","doi-asserted-by":"publisher","award":["#178224"],"award-info":[{"award-number":["#178224"]}],"id":[{"id":"10.13039\/501100015592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Identifying antigens that elicit protective immunity is pivotal for developing effective vaccines and therapeutics against cutaneous leishmaniasis. Dihydrolipoyl dehydrogenase (DLD), a mitochondrial enzyme involved in oxidizing lipoamides to facilitate electron transfer for energy production and metabolism, plays a critical role in virulence of fungi and bacteria. However, its function in\n                    <jats:italic>Leishmania<\/jats:italic>\n                    virulence and pathogenesis remains unexplored. Using a CRISPR-Cas9-based approach, we generated DLD-deficient\n                    <jats:italic>Leishmania (L.) major<\/jats:italic>\n                    parasites and a complementary add-back strain by episomally reintroducing DLD gene into the knockout parasites. Loss of DLD significantly impaired parasite proliferation in axenic cultures and infected macrophages compared to wild-type (WT) and add-back control parasites. These defects were linked to reduced ROS production, impaired mitochondrial permeability, an enhanced oxygen consumption rate, and alterations in mitochondrial ultrastructure. In murine models, DLD-deficient parasites failed to cause observable lesions and exhibited significantly reduced parasite burdens compared to WT and add-back control strains. Notably, mice infected with DLD-deficient parasites displayed blunted immune responses compared to their WT controls. Importantly, vaccination with DLD-deficient parasites conferred robust protection against virulent\n                    <jats:italic>L. major<\/jats:italic>\n                    challenge, characterized by a strong IFN-\u03b3-mediated immune response. These findings establish DLD as an essential metabolic enzyme for\n                    <jats:italic>L. major<\/jats:italic>\n                    intracellular survival and pathogenesis. Targeting DLD not only impairs parasite viability but also holds promise as a novel strategy for vaccine development to combat cutaneous leishmaniasis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012978","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T13:38:20Z","timestamp":1742218700000},"page":"e1012978","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Leishmania major Dihydrolipoyl dehydrogenase (DLD) is a key metabolic enzyme that drives parasite proliferation, pathology and host immune response"],"prefix":"10.1371","volume":"21","author":[{"given":"Somtochukwu S.","family":"Onwah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Mou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patience","family":"Obi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nnamdi","family":"Ikeogu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeid","family":"Ghavami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Saleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2759-0664","authenticated-orcid":true,"given":"Jude","family":"Uzonna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"issue":"5","key":"ppat.1012978.ref001","doi-asserted-by":"crossref","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis 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Schaible","year":"2007","journal-title":"PLoS Medicine"},{"issue":"14","key":"ppat.1012978.ref014","doi-asserted-by":"crossref","first-page":"5502","DOI":"10.1073\/pnas.0509196103","article-title":"Virulence of Leishmania major in macrophages and mice requires the gluconeogenic enzyme fructose-1,6-bisphosphatase","volume":"103","author":"T Naderer","year":"2006","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"10","key":"ppat.1012978.ref015","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1084\/jem.20060559","article-title":"A leishmania amazonensis ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes","volume":"203","author":"C Huynh","year":"2006","journal-title":"Journal of Experimental Medicine"},{"issue":"24","key":"ppat.1012978.ref016","doi-asserted-by":"crossref","first-page":"18555","DOI":"10.1074\/jbc.M110.125393","article-title":"Amplification of adenine 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Protocols"},{"key":"ppat.1012978.ref031","article-title":"Mitochondria","author":"GM Cooper","year":"2000","journal-title":"The Cell: A Molecular Approach"},{"issue":"6","key":"ppat.1012978.ref032","doi-asserted-by":"crossref","first-page":"e1007828","DOI":"10.1371\/journal.ppat.1007828","article-title":"Genetic dissection of a Leishmania flagellar proteome demonstrates requirement for directional motility in sand fly infections","volume":"15","author":"T Beneke","year":"2019","journal-title":"PLoS Pathogens"},{"key":"ppat.1012978.ref033","first-page":"463","article-title":"Trypanosomatids - Methods and Protocols","author":"W-W Zhang","year":"2020","journal-title":"Methods and Protocols"},{"issue":"2","key":"ppat.1012978.ref034","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0166-6851(00)00270-X","article-title":"Episomal and stable expression of the luciferase reporter gene for quantifying Leishmania spp. infections in macrophages and in animal 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implications for vaccine designs and vaccination strategies","volume":"41","author":"I Okwor","year":"2008","journal-title":"Immunology Research"},{"issue":"12","key":"ppat.1012978.ref038","doi-asserted-by":"crossref","first-page":"6967","DOI":"10.4049\/jimmunol.167.12.6967","article-title":"Immune elimination of Leishmania major in mice: Implications for immune memory, vaccination, and reactivation disease","volume":"167","author":"J Uzonna","year":"2001","journal-title":"The Journal of Immunology"},{"issue":"6","key":"ppat.1012978.ref039","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.4049\/jimmunol.172.6.3793","article-title":"Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response","volume":"172","author":"JE Uzonna","year":"2004","journal-title":"The Journal of Immunology"},{"key":"ppat.1012978.ref040","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.3389\/fimmu.2018.01227","article-title":"Translating observations from leishmanization into non-living vaccines: The potential of dendritic cell-based vaccination strategies against Leishmania","volume":"9","author":"N Seyed","year":"2018","journal-title":"Frontiers in Immunology"},{"key":"ppat.1012978.ref041","doi-asserted-by":"crossref","first-page":"105173","DOI":"10.1016\/j.actatropica.2019.105173","article-title":"An overview of leishmanization experience: A successful control measure and a tool to evaluate candidate vaccines","volume":"200","author":"M Mohebali","year":"2019","journal-title":"Acta Tropica"},{"issue":"10","key":"ppat.1012978.ref042","doi-asserted-by":"crossref","first-page":"a038059","DOI":"10.1101\/cshperspect.a038059","article-title":"Long-lived skin-resident memory T cells contribute to concomitant immunity in cutaneous Leishmaniasis","volume":"12","author":"P Scott","year":"2020","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"310","key":"ppat.1012978.ref043","first-page":"310ra166","article-title":"Identification of broadly conserved cross-species protective Leishmania antigen and its responding CD4+ T cells","volume":"7","author":"Z Mou","year":"2015","journal-title":"Science Translational Medicine"},{"key":"ppat.1012978.ref044","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1016\/j.ijbiomac.2020.07.236","article-title":"Mutational studies on Leishmania donovani dihydrolipoamide dehydrogenase (LdBPK291950.1) indicates that the enzyme may not be classical class-I pyridine nucleotide-disulfide oxidoreductase","volume":"164","author":"AK Chiranjivi","year":"2020","journal-title":"International Journal of Biological Macromolecules"},{"issue":"6","key":"ppat.1012978.ref045","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1242\/jcs.056465","article-title":"An exosome-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages","volume":"123","author":"J Silverman","year":"2010","journal-title":"Journal of Cell Science"},{"issue":"6","key":"ppat.1012978.ref046","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1080\/20477724.2016.1232042","article-title":"Pro- and anti-inflammatory cytokines in cutaneous leishmaniasis: a review","volume":"110","author":"N Maspi","year":"2016 Sep","journal-title":"Pathog Glob Health"},{"issue":"11","key":"ppat.1012978.ref047","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1242\/jcs.115.11.2303","article-title":"Biogenesis of Leishmania-harbouring parasitophorus vacuoles following phagocytosis of the metacyclic promastigote or amastigote stages of the parasites","volume":"115","author":"N Courret","year":"2002","journal-title":"Journal of Cell Science"},{"issue":"4","key":"ppat.1012978.ref048","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.pt.2007.02.004","article-title":"Metabolism of Leishmania: proven and predicted","volume":"23","author":"FR Opperdoes","year":"2007","journal-title":"Trends in Parasitology"},{"issue":"9","key":"ppat.1012978.ref049","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.pt.2016.05.005","article-title":"Metabolic crosstalk between Leishmania and the macrophage host","volume":"32","author":"MJ McConville","year":"2016","journal-title":"Trends in Parasitology"},{"issue":"6","key":"ppat.1012978.ref050","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1111\/mmi.13534","article-title":"Glucose deprivation induced upregulation of phosphoenolpyruvate carboxykinase modulates virulence in Leishmania donovani","volume":"102","author":"S Saini","year":"2016","journal-title":"Molecular Microbiology"},{"issue":"3","key":"ppat.1012978.ref051","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1042\/bj1340707","article-title":"The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen","volume":"134","author":"A Boveris","year":"1973","journal-title":"Biochemical Journal"},{"key":"ppat.1012978.ref052","doi-asserted-by":"crossref","first-page":"131641","DOI":"10.1016\/j.snb.2022.131641","article-title":"Analysis of mitochondrial oxygen consumption and hydrogen peroxide release from cardiac mitochondria using electrochemical multi-sensors","volume":"360","author":"M Cheng","year":"2022","journal-title":"Sensors and Actuators B: Chemical"},{"issue":"01","key":"ppat.1012978.ref053","article-title":"The association between physical exercise and reactive oxygen species (ROS) production","volume":"05","author":"AN Nunes","year":"2015","journal-title":"J Sports Med Doping Stud"},{"issue":"2","key":"ppat.1012978.ref054","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1089\/rej.2006.0516","article-title":"Mitochondrial oxygen consumption and reactive oxygen species production are independently modulated: Implications for aging studies","volume":"10","author":"G Barja","year":"2007","journal-title":"Rejuvenation Research"},{"key":"ppat.1012978.ref055","doi-asserted-by":"crossref","first-page":"e24662","DOI":"10.7554\/eLife.24662","article-title":"K\u00fchlbrandt W. Changes of mitochondrial ultrastructure and function during ageing in mice and Drosophila","volume":"6","author":"T Brandt","year":"2017 Jul 12","journal-title":"Elife"},{"issue":"5\u20136","key":"ppat.1012978.ref056","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.bbabio.2006.03.018","article-title":"Effect of oxidative stress on dynamics of mitochondrial reticulum","author":"OY Pletjushkina","year":"2006","journal-title":"Biochim Biophys Acta"},{"issue":"8","key":"ppat.1012978.ref057","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1089\/ars.2007.2000","article-title":"Ultrastructure of the mitochondrion and its bearing on function and bioenergetics","volume":"10","author":"G Benard","year":"2008","journal-title":"Antioxidants & Redox Signaling"},{"issue":"5691","key":"ppat.1012978.ref058","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1126\/science.1100612","article-title":"Mitochondrial fusion intermediates revealed in vitro","volume":"305","author":"S Meeusen","year":"2004","journal-title":"Science"},{"issue":"3","key":"ppat.1012978.ref059","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1158\/0008-5472.CAN-03-1101","article-title":"Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells","volume":"64","author":"R Rossignol","year":"2004","journal-title":"Cancer Research"},{"issue":"4","key":"ppat.1012978.ref060","doi-asserted-by":"crossref","first-page":"C881","DOI":"10.1152\/ajpcell.00104.2005","article-title":"Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency","volume":"289","author":"W Koopman","year":"2005","journal-title":"Am J Physiol Cell Physiol"},{"issue":"2","key":"ppat.1012978.ref061","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1017\/S143192760404005X","article-title":"Altered mitochondrial structure and motion dynamics in living cells 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