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<p>Leishmaniasis is one of the neglected tropical diseases that is endemic to over 90 countries, and its cases are being reported from non-endemic countries as well, like Austria. The cases of&#xa0;visceral leishmaniasis, caused by <i>Leishmania donovani</i> are concentrated on the Indian Subcontinent. There are several studies on the genetic heterogeneity, aneuploidy, and drug resistance emergence from Indian subcontinent as well as globally. However, no research has yet inspected the genomic data from the Indian subcontinent to conduct a comprehensive investigation at the nucleotide level of the genome. We have considered whole-genome sequence data from the publicly available database, i.e., European Nucleotide Archive. Genetic analysis has shown that there is tetraploidy in chromosome 31, trisomy in chromosomes 2 and 8, and trisomy was observed a in chromosomes 6 and 15 among some samples. This aneuploidy pattern is evolving over time as observed in the present study. The&#xa0;paromomycin drug has induced trisomy in chromosome 2. The pattern of aneuploidy variations in samples from the Indian subcontinent differs markedly from that in&#xa0;other continent's samples. Further, ATP-binding cassette family, Amastin-like surface proteins, A2 genes, amino acid permeases, heat shock 70-related protein 1, mitochondrial precursor, putative, partial and sodium stibogluconate resistance protein, putative proteins were those that&#xa0;exhibited the&#xa0;maximum number of mutations amid all the analyzed samples. The proteins showing higher number of mutations belong to membrane proteins that are involved in drug resistance mechanism. Most of these proteins are involved in the virulence and drug resistant mechanism (like transporter proteins). The present study provides the possible candidates which can be targeted to disarm the virulence of the protozoan and drug candidates for therapeutic interventions.</p>

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Insights into genetic heterogeneity and drug resistance in Leishmania donovani of the Indian sub-continent from genomic data

  • 期刊论文

  • 发表日期：

    2025年11月19日

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  • Aroop Verma,
  • Indu Kumari,
  • Anupam Nath Jha

摘要

Leishmaniasis is one of the neglected tropical diseases that is endemic to over 90 countries, and its cases are being reported from non-endemic countries as well, like Austria. The cases of visceral leishmaniasis, caused by Leishmania donovani are concentrated on the Indian Subcontinent. There are several studies on the genetic heterogeneity, aneuploidy, and drug resistance emergence from Indian subcontinent as well as globally. However, no research has yet inspected the genomic data from the Indian subcontinent to conduct a comprehensive investigation at the nucleotide level of the genome. We have considered whole-genome sequence data from the publicly available database, i.e., European Nucleotide Archive. Genetic analysis has shown that there is tetraploidy in chromosome 31, trisomy in chromosomes 2 and 8, and trisomy was observed a in chromosomes 6 and 15 among some samples. This aneuploidy pattern is evolving over time as observed in the present study. The paromomycin drug has induced trisomy in chromosome 2. The pattern of aneuploidy variations in samples from the Indian subcontinent differs markedly from that in other continent's samples. Further, ATP-binding cassette family, Amastin-like surface proteins, A2 genes, amino acid permeases, heat shock 70-related protein 1, mitochondrial precursor, putative, partial and sodium stibogluconate resistance protein, putative proteins were those that exhibited the maximum number of mutations amid all the analyzed samples. The proteins showing higher number of mutations belong to membrane proteins that are involved in drug resistance mechanism. Most of these proteins are involved in the virulence and drug resistant mechanism (like transporter proteins). The present study provides the possible candidates which can be targeted to disarm the virulence of the protozoan and drug candidates for therapeutic interventions.