Browse DORAS
Browse Theses
Search
Latest Additions
Creative Commons License
Except where otherwise noted, content on this site is licensed for use under a:

In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: genomic and metabolomic characterisation

Shaw, C.D. and Lonchamp, J. and Downing, Tim and Imamura, Hideo (2016) In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: genomic and metabolomic characterisation. Molecular Microbiology, 99 (6). pp. 1134-1148. ISSN 1365-2958

Full text available as:

[img]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1670Kb

Abstract

In this study we followed the genomic, lipidomic and metabolomic changes associated with the selection of miltefosine (MIL) resistance in two clinically derived L. donovani strains with different inherent resistance to antimonial drugs (antimony sensitive strain Sb-S; and antimony resistant Sb-R). MIL-R was easily induced in both strains using the promastigotestage, but a significant increase in MIL-R in the intracellular amastigote compared to the corresponding WT did not occur until promastigotes had adapted to 12.2 µM MIL. A variety of common and strain-specific genetic changes were discovered in MIL-adapted parasites, including deletions at the LdMT transporter gene, single-base mutations and changes in somy. The most obvious lipid changes in MIL-R promastigotes occurred to phosphatidylcholines and lysophosphatidylcholines and results indicate that the Kennedy pathway is involved in MIL resistance. The inherent Sb resistance of the parasite had an impact on the changes that occurred in MIL-R parasites, with more genetic changes occurring in Sb-R compared to Sb-S parasites. Initial interpretation of the changes identified in this study does not support synergies with Sb-R in the mechanisms of MIL resistance, though this requires an enhanced understanding of the parasite’s biochemical pathways and how they are genetically regulated to be verified fully.

Item Type:Article (Published)
Refereed:Yes
Subjects:Biological Sciences > Genetics
Biological Sciences > Bioinformatics
Biological Sciences > Microbiology
Biological Sciences > Biochemistry
Biological Sciences > Molecular biology
DCU Faculties and Centres:Research Initiatives and Centres > Scientific Computing and Complex Systems Modelling (Sci-Sym)
DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Publisher:Blackwell Publishing
Official URL:http://dx.doi.org/10.1111/mmi.13291
Copyright Information:© 2015 Wiley Blackwell
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 License. View License
ID Code:21055
Deposited On:28 Jan 2016 11:45 by Tim Downing. Last Modified 29 Dec 2016 01:02

Download statistics

Archive Staff Only: edit this record