Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent

Imamura, H. et al. (2016) Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent. eLife, 5, e12613. (doi:10.7554/eLife.12613) (PMID:27003289) (PMCID:PMC4811772)

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Abstract

Leishmania donovani causes visceral leishmaniasis (VL), the second most deadly vector-borne parasitic disease. A recent epidemic in the Indian subcontinent (ISC) caused up to 80% of global VL and over 30,000 deaths per year. Resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. Here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of L. donovani from the ISC. We identify independent radiations that have emerged since a bottleneck coincident with 1960s DDT spraying campaigns. A genetically distinct population frequently resistant to antimonials has a two base-pair insertion in the aquaglyceroporin gene LdAQP1 that prevents the transport of trivalent antimonials. We find evidence of genetic exchange between ISC populations, and show that the mutation in LdAQP1 has spread by recombination. Our results reveal the complexity of L. donovani evolution in the ISC in response to drug treatment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:De Koning, Professor Harry and Settimo, Dr Luca
Authors: Imamura, H., Downing, T., Van den Broeck, F., Sanders, M. J., Rijal, S., Sundar, S., Mannaert, A., Vanaerschot, M., Berg, M., De Muylder, G., Dumetz, F., Cuypers, B., Maes, I., Domagalska, M., Decuypere, S., Rai, K., Uranw, S., Bhattarai, N. R., Khanal, B., Prajapati, V. K., Sharma, S., Stark, O., Schönian, G., De Koning, H. P., Settimo, L., Vanhollebeke, B., Roy, S., Ostyn, B., Boelaert, M., Maes, L., Berriman, M., Dujardin, J.-C., and Cotton, J. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Published Online:22 March 2016
Copyright Holders:Copyright © 2016 Imamura et al.
First Published:First published in eLife 5: e12613
Publisher Policy:Reproduced under a Creative Commons License

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