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In this manuscript, we report that zinc (Zn) chelator N,N,N\u2019,N\u2019-tetrakis(2-pyridinylmethyl)-1,2-ethylenediamine (TPEN) affects growth and viability of intracellular pathogen <jats:italic>Leishmania donovani<\/jats:italic> (LD) by a concentration and time dependent manner. Simultaneous addition of zinc salt reverses the effect of TPEN. Further experiments provide evidence of apoptosis-like death of the parasite due to Zn-depletion. TPEN treatment enhances caspase-like activity suggesting increase in apoptosis-like events in LD. Specific inhibitors of cathepsin B and Endoclease G block TPEN-induced leishmanial death. Evidences show involvement of reactive oxygen species (ROS) potentially of extra-mitochondrial origin in TPEN-induced LD death. Pentavalent antimonials remained the prime source of treatment against leishmaniasis for several decades; however, antimony-resistant <jats:italic>Leishmania<\/jats:italic> is now common source of the disease. We also reveal that Zn-depletion can promote apoptosis-like death in antimony-resistant parasites. In summary, we present a new finding about the role of zinc in the survival of drug sensitive and antimony-resistant LD.<\/jats:p>","DOI":"10.1038\/s41598-017-10041-6","type":"journal-article","created":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T10:56:09Z","timestamp":1504090569000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani"],"prefix":"10.1038","volume":"7","author":[{"given":"Shalini","family":"Saini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Bharati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrima","family":"Shaha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinmay K.","family":"Mukhopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,5]]},"reference":[{"key":"10041_CR1","doi-asserted-by":"publisher","first-page":"875","DOI":"10.3390\/nu4080875","volume":"4","author":"S Alam","year":"2012","unstructured":"Alam, S. & Kelleher, S. 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