Oxidative Stress-Mediated Overexpression of Uracil DNA Glycosylase in Leishmania donovani Confers Tolerance against Antileishmanial Drugs
Joint Authors
Mishra, Anshul
Khan, Mohd. Imran
Jha, Pravin K.
Kumar, Ajay
Das, Sushmita
Das, Prolay
Sinha, Kislay K.
Das, Pradeep
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-21, 21 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-02-25
Country of Publication
Egypt
No. of Pages
21
Main Subjects
Abstract EN
Leishmania donovani 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’s capacity to cope up with highly oxidative environment.
Base excision repair (BER) pathway in L.
donovani remains unexplored.
We studied uracil DNA glycosylase (UNG), the key enzyme involved in BER pathway, and found that the glycosylase activity of recombinant LdUNG (Leishmania donovani UNG) expressed in E.
coli 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.
American Psychological Association (APA)
Mishra, Anshul& Khan, Mohd. Imran& Jha, Pravin K.& Kumar, Ajay& Das, Sushmita& Das, Prolay…[et al.]. 2018. Oxidative Stress-Mediated Overexpression of Uracil DNA Glycosylase in Leishmania donovani Confers Tolerance against Antileishmanial Drugs. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-21.
https://search.emarefa.net/detail/BIM-1211376
Modern Language Association (MLA)
Mishra, Anshul…[et al.]. Oxidative Stress-Mediated Overexpression of Uracil DNA Glycosylase in Leishmania donovani Confers Tolerance against Antileishmanial Drugs. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-21.
https://search.emarefa.net/detail/BIM-1211376
American Medical Association (AMA)
Mishra, Anshul& Khan, Mohd. Imran& Jha, Pravin K.& Kumar, Ajay& Das, Sushmita& Das, Prolay…[et al.]. Oxidative Stress-Mediated Overexpression of Uracil DNA Glycosylase in Leishmania donovani Confers Tolerance against Antileishmanial Drugs. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-21.
https://search.emarefa.net/detail/BIM-1211376
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1211376