Login (DCU Staff Only)
Login (DCU Staff Only)

DORAS | DCU Research Repository

Explore open access research and scholarly works from DCU

Advanced Search

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

Shaw, C.D., Lonchamp, J., 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

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.
Metadata
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 19 Jul 2018 15:07
Documents

Full text available as:

[thumbnail of ShawLongchampDowningImamuraEtAl2016-MolMicrobiol.pdf]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB
Downloads

Downloads

Downloads per month over past year

Archive Staff Only: edit this record