Projects per year
Abstract
Leishmania infantum is an etiological agent of the life-threatening visceral form of leishmaniasis. Liposomal amphotericin B (AmB) followed by a short administration of miltefosine (MF) is a drug combination effective for treating visceral leishmaniasis in endemic regions of India. Resistance to MF can be due to point mutations in the miltefosine transporter (MT). Here we show that mutations in MT are also observed in Leishmania AmB-resistant mutants. The MF-induced MT mutations, but not the AmB induced mutations in MT, alter the translocation/uptake of MF. Moreover, mutations in the MT selected by AmB or MF have a major impact on lipid species that is linked to cross-resistance between both drugs. These alterations include changes of specific phospholipids, some of which are enriched with cyclopropanated fatty acids, as well as an increase in inositolphosphoceramide species. Collectively these results provide evidence of the risk of cross-resistance emergence derived from current AmB-MF sequential or co-treatments for visceral leishmaniasis.
Original language | English |
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Article number | e0005171 |
Number of pages | 20 |
Journal | PLoS Neglected Tropical Diseases |
Volume | 10 |
Issue number | 12 |
DOIs | |
Publication status | Published - 2 Dec 2016 |
Keywords
- Lipids
- Leishmania infantum
- Fatty acids
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Dive into the research topics of 'Different mutations in a P-type ATPase transporter in Leishmania parasites are associated with cross-resistance to two leading drugs by distinct mechanisms'. Together they form a unique fingerprint.Projects
- 2 Finished
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Investigating Trypanosoma brucei's: Investigating Trypanosoma Brucei's Unusual Inositol Metabolism
Smith, T. K. (PI)
1/01/11 → 31/03/14
Project: Standard
Profiles
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Terry K Smith
- School of Biology - Director of Biomedical Sciences Research Complex, Professor
- Sir James Mackenzie Institute for Early Diagnosis
- Biomedical Sciences Research Complex
Person: Academic
Datasets
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Different mutations in a P-type ATPase transporter in Leishmania parasites are associated with cross-resistance to two leading drugs by distinct mechanisms (dataset)
Fernandez-Prada, C. (Creator), Vincent, I. M. (Creator), Brotherton, M.-C. (Creator), Roberts, M. (Creator), Roy, G. (Creator), Rivas, L. (Creator), Leprohon, P. (Creator), Smith, T. K. (Creator) & Ouellette, M. (Creator), Figshare, 2016
Dataset