Abstract
BackgroundLeishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. Despite the advances in molecular biology and the availability of more Leishmania genome references in recent years, the association between parasite species and distinct clinical phenotypes remains poorly understood. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis.ResultsClinical isolates from six cutaneous leishmaniasis patients (CL-SL); 2 of whom were poor responders to antimony (CL-PR), and two visceral leishmaniasis patients (VL-SL) were sequenced on an Illumina MiSeq platform. Chromosome aneuploidy was observed in both groups but was more frequent in CL-SL. 248 genes differed by 2 fold or more in copy number among the two groups. Genes involved in amino acid use (LdBPK_271940) and energy metabolism (LdBPK_271950), predominated the VL-SL group with the same distribution pattern reflected in gene tandem arrays. Genes encoding amastins were present in higher copy numbers in VL-SL and CL-PR as well as being among predicted pseudogenes in CL-SL. Both chromosome and SNP profiles showed CL-SL and VL-SL to form two distinct groups. While expected heterozygosity was much higher in VL-SL, SNP allele frequency patterns did not suggest potential recent recombination breakpoints. The SNP/indel profile obtained using the more recently generated PacBio sequence did not vary markedly from that based on the standard LdBPK282A1 reference. Several genes previously associated with resistance to antimonials were observed in higher copy numbers in the analysis of CL-PR. H-locus amplification was seen in one cutaneous isolate which however did not belong to the CL-PR group.ConclusionsThe data presented suggests that intra species variations at chromosome and gene level are more likely to influence differences in tropism as well as response to treatment, and contributes to greater understanding of parasite molecular mechanisms underpinning these differences. These findings should be substantiated with a larger sample number and expression/functional studies.
Highlights
Leishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions
Using generation sequencing technologies, we describe here the genomic diversity of 8 clinical isolates of L. donovani from Sri Lanka; which included 2 isolates from patients diagnosed with visceral leishmaniasis (VL) and 6 isolates from patients diagnosed with cutaneous leishmaniasis (CL)
The six cutaneous leishmaniasis (CL-SL) and two visceral leishmaniasis (VL-SL) clinical isolates were from patients originating from different regions of the country (Additional file 1: Table S1-(A))
Summary
Leishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis. Leishmaniasis is a neglected tropical disease with spread across 98 countries over five continents. The same parasite species has been known to cause different clinical phenotypes. This complexity of the disease poses many challenges to control efforts which are further compounded by variable responses to drugs, across continents but even within the same region. While the resulting phenotype is influenced by the interactions between the parasite, susceptible host and vector as well as the environment, a more severe degree of pathogenicity such as involvement of viscera and drug resistance are considered to be virulent features largely determined by parasite genotypes
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