Integrated genomic and metabolomic profiling of ISC1, an emerging Leishmania donovani population in the Indian subcontinent

Bart Cuypers,Maya Berg,Hideo Imamura,Franck Dumetz,Géraldine De Muylder,Malgorzata A Domagalska,Suman Rijal,Narayan Raj Bhattarai,Ilse Maes,Mandy Sanders,James A Cotton,Pieter Meysman,Kris Laukens,Jean-Claude Dujardin

doi:10.1016/j.meegid.2018.04.021

Abstract

Leishmania donovani is the responsible agent for visceral leishmaniasis (VL) in the Indian subcontinent (ISC). The disease is lethal without treatment and causes 0.2 to 0.4 million cases each year. Recently, reports of VL in Nepalese hilly districts have increased as well as VL cases caused by L. donovani from the ISC1 genetic group, a new and emerging genotype. In this study, we perform for the first time an integrated, untargeted genomics and metabolomics approach to characterize ISC1, in comparison with the Core Group (CG), main population that drove the most recent outbreak of VL in the ISC. We show that the ISC1 population is very different from the CG, both at genome and metabolome levels. The genomic differences include SNPs, CNV and small indels in genes coding for known virulence factors, immunogens and surface proteins. Both genomic and metabolic approaches highlighted dissimilarities related to membrane lipids, the nucleotide salvage pathway and the urea cycle in ISC1 versus CG. Many of these pathways and molecules are important for the interaction with the host/extracellular environment. Altogether, our data predict major functional differences in ISC1 versus CG parasites, including virulence. Therefore, particular attention is required to monitor the fate of this emerging ISC1 population in the ISC, especially in a post-VL elimination context.

Highlights

Visceral Leishmaniasis (VL) or kala-azar is a neglected tropical disease globally responsible for 0.2 to 0.4 million cases each year (Alvar et al, 2012)
In correspondence with Imamura et al (2016) (Imamura et al, 2016), this showed that (i) ISC1 parasites cluster at a larger distance from Core Group (CG) than the Sri Lanka strain SRI-CLB and (ii) in an intermediate position with respect to East African L. donovani LV9
In this work we have performed a genomic and metabolic profiling study of strains representing ISC1, a new Leishmania donovani population that is currently emerging in Nepal

Summary

Introduction

Visceral Leishmaniasis (VL) or kala-azar is a neglected tropical disease globally responsible for 0.2 to 0.4 million cases each year (Alvar et al, 2012). The disease is lethal without treatment and caused by protozoan parasites of the Leishmania donovani complex. In the Indian subcontinent (ISC), VL is of major concern for public health with > 200 million people at risk (Ostyn et al, 2011). The recent whole-genome sequencing and phylogenomic analysis of 204 Leishmania strains from the ISC (India, Nepal and Bangladesh), revealed that the most recent VL epidemic in this region were essentially driven by one large L. donovani population that emerged around 1850 and spread across the lowlands in the Ganges plain. This population is genetically very homogeneous (Imamura et al, 2016) and was called the Core Group (CG)

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Conclusion