What is it about?
In previous a previous study on the genome diversity of L. donovani in the ISC we described 2 distinct groups notably the ISC1 in the Indo-Napalese highlands and the core group (CG) in low land of India, Nepal and Bangladesh (Imamura et al. 2016). In the present study we decided to look at a different biological level, the metabolome and to integrate it with the genome. To do so we used 5 isolates from the ISC1 group and 4 from the CG to perform a new whole genome sequencing and the metabolomic profiling. From the genomic work we would clearly characterise the presence of variants in the ISC1 group compare to the reference genome (BPK282) and evaluate their potential effect on the biology of the parasite. We characterised further the different gene copy number variations that is one of the feature of Leishmania. The metabolome study allowed us to assess the homogeneity of the CG isolates at this level as well (isolates from the CG are genetically very close) while the ISC1 isolates were more diverse in that particular aspect (fitting with the genome study). And for the first time in Leishmania field we could integrate the genome and the metabolome linking the genomic dissimilarity to the metabolomic one.
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Why is it important?
A deeper understanding of the biology of the ISC1 group is needed since it was demonstrated in 2016 that the parasite belonging to the ISC1 population are expending in Nepal (Rai et al. PLoS NTD). Until then the CG was the majority of the parasites found in that particular country and in the rest of the ISC. The CG has been weel studied for its capacity to resist to antimonials but also to manipulate the host immune system. So far very few to none is known about ISC1. To be able to fight a spreading parasite we have to know where they come from, how they behave in the wild and how they respond to treatment. This study is the first one applying an integrative approach to apprehend the ISC1 in comparison to its closest relative the CG.
Perspectives
After this global view of the ISC1 group more remains to be done especially in the aspect of the susceptibility to the different anti-Leishmania compounds that are available. A new study demonstrate that the ISC1 isolates are far more susceptible to antimonials but also that the same type of adaptation than the one from CG to resist to antimonials was put in place (Dumetz et al. mSphere). Antimonials are not in use in the pharmacopoeia anymore and nothing is none about the ISC1 susceptibitily to other drugs like miltefosine or amphotericine B neither if they could be pre-adaptated to resist to these drugs. Nothing is none about their clinical manifestation or their particular tissue tropism so this still remains to be investigated. And finally there ability to divert the host immune system is poorly understand while it was already demonstrated that antimony resistant CG isolates are masters when it comes to manipulate the host.
Dr Franck Dumetz
University of Maryland
Read the Original
This page is a summary of: Integrated genomic and metabolomic profiling of ISC1, an emerging Leishmania donovani population in the Indian subcontinent, Infection Genetics and Evolution, April 2018, Elsevier,
DOI: 10.1016/j.meegid.2018.04.021.
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Resources
Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent
Article describing the genetic structure of the L. donovani population on the Indian subcontinent. This article is the fondation of all the research performed on the different groups of Leishmania donovani from the ISC.
Molecular preadaptation to antimony resistance in Leishmania donovani on the Indian subcontinent
First description of a natural pre-adaptation to antimony in Leishmania. In this article we demonstrate at all the isolates from the Indo-Nepalese lowlands (CG) are pre-adaptated to antimony due to there intra-chromosomal amplification of the H-locus and more particularly of MRPA. On the opposite, the isolates from the Nepalese highlands (ISC1 group) are not pre-adapted and very sensitive to antimony.
New "Yeti"-variant of visceral leishmaniasis parasite discovered
Institutional press release
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