Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent

被引:119
作者
Imamura, Hideo [1 ]
Downing, Tim [2 ,3 ,14 ]
Van den Broeck, Frederik [1 ]
Sanders, Mandy J. [2 ]
Rijal, Suman [4 ]
Sundar, Shyam [5 ]
Mannaert, An [1 ]
Vanaerschot, Manu [1 ,15 ]
Berg, Maya [1 ]
De Muylder, Geraldine [1 ]
Dumetz, Franck [1 ]
Cuypers, Bart [1 ]
Maes, Ilse [1 ]
Domagalska, Malgorzata [1 ]
Decuypere, Saskia [1 ,6 ]
Rai, Keshav [4 ,16 ]
Uranw, Surendra [4 ]
Bhattarai, Narayan Raj [4 ]
Khanal, Basudha [4 ]
Prajapati, Vijay Kumar [5 ,17 ]
Sharma, Smriti [5 ]
Stark, Oilvia [7 ]
Schoenian, Gabriele [7 ]
De Koning, Harry P. [8 ]
Settimo, Luca [8 ,9 ]
Vanhollebeke, Benoit [10 ]
Roy, Syamal [11 ]
Ostyn, Bart [12 ]
Boelaert, Marleen [12 ]
Maes, Louis [13 ]
Berriman, Matthew [2 ]
Dujardin, Jean-Claude [1 ,13 ]
Cotton, James A. [2 ]
机构
[1] Inst Trop Med, Dept Biomed Sci, B-2000 Antwerp, Belgium
[2] Wellcome Trust Sanger Inst, Hinxton, England
[3] Natl Univ Ireland Galway, Sch Math Appl Math & Stat, Galway, Ireland
[4] BP Koirala Inst Hlth Sci, Dharan, Nepal
[5] Banaras Hindu Univ, Inst Med Sci, Dept Med, Varanasi 221005, Uttar Pradesh, India
[6] Univ Western Australia, Telethon Kids Inst, Perth, WA 6009, Australia
[7] Charite, Inst Mikrobiol & Hyg, D-13353 Berlin, Germany
[8] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland
[9] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA
[10] Univ Libre Bruxelles, Mol Parasitol Lab, Gosselies, Belgium
[11] Indian Inst Chem Biol, Dept Infect Dis & Immunol, Council Sci & Ind Res, Kolkata, India
[12] Inst Trop Med, Dept Publ Hlth, B-2000 Antwerp, Belgium
[13] Univ Antwerp, Dept Biomed Sci, Fac Pharmaceut Biomed & Vet Sci, B-2020 Antwerp, Belgium
[14] Dublin City Univ, Sch Biotechnol, Dublin 9, Ireland
[15] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, 630 W 168th St, New York, NY 10032 USA
[16] West Bengal State Univ, Kolkata, India
[17] Cent Univ Rajasthan, Dept Biochem, Ajmer, India
基金
英国惠康基金;
关键词
DRUG-RESISTANCE; KALA-AZAR; DELETERIOUS MUTATIONS; POPULATION-STRUCTURE; VARIATION DISCOVERY; DONOVANI COMPLEX; GENERATION; ANTIMONY; NUMBER; DISEQUILIBRIUM;
D O I
10.7554/eLife.12613
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:39
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