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Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811772/
https://www.ncbi.nlm.nih.gov/pubmed/27003289
http://dx.doi.org/10.7554/eLife.12613
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author 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
author_facet 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
author_sort Imamura, Hideo
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.12613.001
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spelling pubmed-48117722016-04-04 Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent 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 eLife Epidemiology and Global Health 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. DOI: http://dx.doi.org/10.7554/eLife.12613.001 eLife Sciences Publications, Ltd 2016-03-22 /pmc/articles/PMC4811772/ /pubmed/27003289 http://dx.doi.org/10.7554/eLife.12613 Text en © 2016, Imamura et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Epidemiology and Global Health
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
Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent
title Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent
title_full Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent
title_fullStr Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent
title_full_unstemmed Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent
title_short Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent
title_sort evolutionary genomics of epidemic visceral leishmaniasis in the indian subcontinent
topic Epidemiology and Global Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811772/
https://www.ncbi.nlm.nih.gov/pubmed/27003289
http://dx.doi.org/10.7554/eLife.12613
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