Picture child's feet next to pens, pencils and paper

Open Access research that is helping to improve educational outcomes for children

Strathprints makes available scholarly Open Access content by researchers in the School of Education, including those researching educational and social practices in curricular subjects. Research in this area seeks to understand the complex influences that increase curricula capacity and engagement by studying how curriculum practices relate to cultural, intellectual and social practices in and out of schools and nurseries.

Research at the School of Education also spans a number of other areas, including inclusive pedagogy, philosophy of education, health and wellbeing within health-related aspects of education (e.g. physical education and sport pedagogy, autism and technology, counselling education, and pedagogies for mental and emotional health), languages education, and other areas.

Explore Open Access education research. Or explore all of Strathclyde's Open Access research...

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

Shaw, C. D. and Lonchamp, J. and Downing, T. and Imamura, H. and Freeman, T. M. and Cotton, J. A. and Sanders, M. and Blackburn, G. and Dujardin, J. C. and Rijal, S. and Khanal, B. and Illingworth, C. J. R. and Coombs, G. H. and Carter, K. C. (2016) In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal : genomic and metabolomic characterization. Molecular Microbiology, 99 (6). pp. 1134-1148. ISSN 0950-382X

[img] Text (Shaw-et-al-MM-2016-In-vitro-selection-of-miltefosine-resistance-in-promastigotes-of-Leishmania)
Shaw_et_al_MM_2016_In_vitro_selection_of_miltefosine_resistance_in_promastigotes_of_Leishmania.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo

Download (878kB)

Abstract

n this study, we followed the genomic, lipidomic and metabolomic changes associated with the selection of miltefosine (MIL) resistance in two clinically derived Leishmania 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 promastigote-stage, but a significant increase in MIL-R in the intracellular amastigote compared to the corresponding wild-type 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 with 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.