Authors

J A Cotton⁴; M Domagalska³; H Imamura³; S Franssen⁴; F Van den Broeck³; C Durrant⁴; T Downing²; M J Sanders⁴; O Stark¹; B Moser¹; G Schönian¹; M Berriman⁴; J C Dujardin³;  ¹ Charité Universitätsmedizin, Germany;  ² Dublin City University, Ireland;  ³ Institute of Tropical Medicine, Antwerp, Belgium;  ⁴ Wellcome Trust Sanger Institute

Discussion

Genomic data is starting to provide unprecedented resolution of the genetics of Leishmania populations. We show that whole-genome sequence data clarifies the evolution of the Leishmania donovani complex, and shows that different populations of visceral leishmaniasis pathogens have strikingly different population genetics, differing in genetic diversity and in the amount of recombination occurring. In our most detailed study, focusing on the Indian subcontinent (ISC), we show that genome data can resolve population structure associated with changes in drug sensitivity that is invisible to traditional molecular markers and can identify molecular variants potentially associated with reduced efficacy of antimonial drugs in that setting. These data should set the scene for genetic surveillance of the Leishmania population in the ISC, providing valuable support for disease control efforts. To-date, our data have all been generated from isolates in culture, but to make surveillance possible, we need to be able to generate genomic data for parasites directly from patient clinical samples. We show that an enrichment strategy using oligonucleotide baits allows us to sequence essentially the entire Leishmania genome from patient bone marrow samples. Taken together, our database of L. donovani genome variation and this technical advance moves Leishmania genomics close to being a clinically useful tool.