Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent

Hideo Imamura, Tim Downing, Frederik Van den Broeck, Mandy J Sanders, Suman Rijal, Shyam Sundar, An Mannaert, Manu Vanaerschot, Maya Berg, Géraldine De Muylder, Franck Dumetz, Bart Cuypers, Ilse Maes, Malgorzata Domagalska, Saskia Decuypere, Keshav Rai, Surendra Uranw, Narayan Raj Bhattarai, Basudha Khanal, Vijay Kumar PrajapatiSmriti Sharma, Olivia Stark, Gabriele Schönian, Harry P De Koning, Luca Settimo, Benoit Vanhollebeke, Syamal Roy, Bart Ostyn, Marleen Boelaert, Louis Maes, Matthew Berriman, Jean-Claude Dujardin, James A Cotton

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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.
Original languageEnglish
JournaleLIFE
Volume5
Pages (from-to)e12613
Number of pages39
ISSN2050-084X
DOIs
Publication statusPublished - 2016

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