Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent

Author:

Imamura Hideo1,Downing Tim23ORCID,Van den Broeck Frederik1ORCID,Sanders Mandy J2,Rijal Suman4,Sundar Shyam5,Mannaert An1,Vanaerschot Manu1,Berg Maya1,De Muylder Géraldine1,Dumetz Franck1,Cuypers Bart1,Maes Ilse1,Domagalska Malgorzata1,Decuypere Saskia16,Rai Keshav4ORCID,Uranw Surendra4,Bhattarai Narayan Raj4,Khanal Basudha4,Prajapati Vijay Kumar5,Sharma Smriti5,Stark Olivia7,Schönian Gabriele7,De Koning Harry P8ORCID,Settimo Luca89,Vanhollebeke Benoit10ORCID,Roy Syamal11,Ostyn Bart12,Boelaert Marleen12ORCID,Maes Louis13,Berriman Matthew2ORCID,Dujardin Jean-Claude113,Cotton James A2ORCID

Affiliation:

1. Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium

2. Wellcome Trust Sanger Institute, Hinxton, United Kingdom

3. School of Maths, Applied Maths and Statistics, National University of Ireland Galway, Galway, Ireland

4. BP Koirala Institute of Health Sciences, Dharan, Nepal

5. Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

6. Telethon Kids Institute, University of Western Australia, Perth, Australia

7. Institut für Mikrobiologie und Hygiene, Charité Universitätsmedizin Berlin, Berlin, Germany

8. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

9. Department of Chemistry and Chemical Biology, Northeastern University, Boston, United States

10. Laboratory of Molecular Parasitology, Université Libre de Bruxelles, Gosselies, Belgium

11. Department of Infectious Diseases and Immunology, Council of Scientific and Industrial Research, Indian Institute of Chemical Biology, Kolkata, India

12. Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium

13. Department of Biomedical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium

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.

Funder

European Commission

Belgian Science Policy Office

Flemish Fund for Scientific Research

Department of Economy, Science and Innovation in Flanders

Wellcome Trust

Belgian Development Cooperation

INBEV-Baillet Latour Foundation

JC Bose National Fellowship, DST, Government of India

Council of Scientific and Industrial Research

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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