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

Research output: Contribution to journalA1: Web of Science-article

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.

Original languageEnglish
JournalInfection, Genetics and Evolution
Volume62
Pages (from-to)170-178
Number of pages9
ISSN1567-1348
DOIs
Publication statusPublished - 2018

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