Evolutionary genomics of epidemic visceral leishmaniasis in the indian subcontinent
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2016-03-22Author
Imamura, Hideo
Downing, Tim
Van den Broeck, Frederik
Sanders, Mandy J
Rijal, Suman
Sundar, Shyam
Mannaert, An
Vanaerschot, Manu
Berg, Maya
De Muylder, Géraldine
Dumetz, Franck
Cuypers, Bart
Maes, Ilse
Domagalska, Malgorzata
Decuypere, Saskia
Rai, Keshav
Uranw, Surendra
Bhattarai, Narayan Raj
Khanal, Basudha
Prajapati, Vijay Kumar
Sharma, Smriti
Stark, Olivia
Schönian, Gabriele
De Koning, Harry P
Settimo, Luca
Vanhollebeke, Benoit
Roy, Syamal
Ostyn, Bart
Boelaert, Marleen
Maes, Louis
Berriman, Matthew
Dujardin, Jean-Claude
Cotton, James A
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Imamura, Hideo; Downing, Tim; Van den Broeck, Frederik; Sanders, Mandy J; Rijal, Suman; Sundar, Shyam; Mannaert, An; Vanaerschot, Manu; Berg, Maya; De Muylder, Géraldine; Dumetz, Franck; Cuypers, Bart; Maes, Ilse; Domagalska, Malgorzata; Decuypere, Saskia; Rai, Keshav; Uranw, Surendra; Bhattarai, Narayan Raj; Khanal, Basudha; Prajapati, Vijay Kumar; Sharma, Smriti; Stark, Olivia; Schönian, Gabriele; De Koning, Harry P; Settimo, Luca; Vanhollebeke, Benoit; Roy, Syamal; Ostyn, Bart; Boelaert, Marleen; Maes, Louis; Berriman, Matthew; Dujardin, Jean-Claude; Cotton, James A (2016). Evolutionary genomics of epidemic visceral leishmaniasis in the indian subcontinent. eLife 5 ,
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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.