| Literature DB >> 27003289 |
Hideo Imamura1, Tim Downing2,3, Frederik Van den Broeck1, Mandy J Sanders2, Suman Rijal4, Shyam Sundar5, An Mannaert1, Manu Vanaerschot1, Maya Berg1, Géraldine De Muylder1, Franck Dumetz1, Bart Cuypers1, Ilse Maes1, Malgorzata Domagalska1, Saskia Decuypere1,6, Keshav Rai4, Surendra Uranw4, Narayan Raj Bhattarai4, Basudha Khanal4, Vijay Kumar Prajapati5, Smriti Sharma5, Olivia Stark7, Gabriele Schönian7, Harry P De Koning8, Luca Settimo8,9, Benoit Vanhollebeke10, Syamal Roy11, Bart Ostyn12, Marleen Boelaert12, Louis Maes13, Matthew Berriman2, Jean-Claude Dujardin1,13, James A Cotton2.
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.Entities:
Keywords: epidemiology; evolution; genomics; global health; infectious disease; leishmania donovani; microbiology
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Year: 2016 PMID： 27003289 PMCID： PMC4811772 DOI： 10.7554/eLife.12613
Source DB: PubMed Journal: Elife ISSN： 2050-084X Impact factor: 8.140