{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:26:53Z","timestamp":1787970413049,"version":"build-2784847793"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,2,25]],"date-time":"2018-02-25T00:00:00Z","timestamp":1519516800000},"content-version":"vor","delay-in-days":55,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001850","name":"Department of Chemicals and Petrochemicals, Ministry of Chemicals and Fertilizers, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p><jats:italic>Leishmania donovani<\/jats:italic> is an intracellular protozoan parasite that causes endemic tropical disease visceral leishmaniasis (VL). Present drugs used against this fatal disease are facing resistance and toxicity issues. Survival of leishmania inside the host cells depends on the parasite\u2019s capacity to cope up with highly oxidative environment. Base excision repair (BER) pathway in <jats:italic>L. donovani<\/jats:italic> remains unexplored. We studied uracil DNA glycosylase (UNG), the key enzyme involved in BER pathway, and found that the glycosylase activity of recombinant LdUNG (<jats:italic>Leishmania donovani<\/jats:italic> UNG) expressed in <jats:italic>E. coli<\/jats:italic> is in sync with the activity of the parasite lysate under different reaction conditions. Overexpression of UNG in the parasite enhances its tolerance towards various agents which produce reactive oxygen species (ROS) and shows a higher infectivity in macrophages. Surprisingly, exposure of parasite to amphotericin B and sodium antimony gluconate upregulates the expression of UNG. Further, we found that the drug resistant parasites isolated from VL patients show higher expression of UNG. Mechanisms of action of some currently used drugs include accumulation of ROS. Our findings strongly suggest that targeting LdUNG would be an attractive therapeutic strategy as well as potential measure to tackle the problem of drug resistance in the treatment of leishmaniasis.<\/jats:p>","DOI":"10.1155\/2018\/4074357","type":"journal-article","created":{"date-parts":[[2018,2,25]],"date-time":"2018-02-25T23:31:48Z","timestamp":1519601508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Oxidative Stress\u2010Mediated Overexpression of Uracil DNA Glycosylase in <i>Leishmania donovani<\/i> Confers Tolerance against Antileishmanial Drugs"],"prefix":"10.1155","volume":"2018","author":[{"given":"Anshul","family":"Mishra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd. 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