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

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 last outbreak of VL in the ISC. We show that the ISC1 population is very different from the CG, both at genome and metabolome levels. These differences included 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 parasites, including virulence. Therefore, particular attention is required to monitor the fate of this emerging population in the ISC, especially in a post-VL elimination context.

Jaar van publicatie:2018

Trefwoorden:A1 Journal article

BOF-keylabel:ja

BOF-publication weight:2

CSS-citation score:1

Auteurs:International

Authors from:Government

Toegankelijkheid:Open