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Review
. 2023 Feb 6:13:1001973.
doi: 10.3389/fcimb.2023.1001973. eCollection 2023.

The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective

Mohd Kamran  1 , Rahul Bhattacharjee  1 , Sonali Das  1 , Sohitri Mukherjee  1 , Nahid Ali  1
Affiliations
Review

The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective

Mohd Kamran et al. Front Cell Infect Microbiol. .

Abstract

Leishmania is an intracellular, zoonotic, kinetoplastid eukaryote with more than 1.2 million cases all over the world. The leishmanial chromosomes are divided into polymorphic chromosomal ends, conserved central domains, and antigen-encoding genes found in telomere-proximal regions. The genome flexibility of chromosomal ends of the leishmanial parasite is known to cause drug resistance and intracellular survival through the evasion of host defense mechanisms. Therefore, in this review, we discuss the plasticity of Leishmania genome organization which is the primary cause of drug resistance and parasite survival. Moreover, we have not only elucidated the causes of such genome plasticity which includes aneuploidy, epigenetic factors, copy number variation (CNV), and post-translation modification (PTM) but also highlighted their impact on drug resistance and parasite survival.

Keywords: drug resistance; genome organization; leishmania; parasite survival; plasticity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Genomic organization of leishmanial parasites and its regulation of Copy number variation to modulate and influence drug resistance and parasite survival. The leishmanial species contains 34-36 chromosomes where a vast polycistronic unit spans through the protein-coding genes with a size from 0.3 to 2.8 mb. The transcription of these lengthy polycistronic units occurs bi-directionally from the start sites situated at switch regions of the strand.
Figure 2
Figure 2
A molecular understanding of drug resistance caused by leishmanial parasite. Copy number variation influences drug resistance through single nucleotide polymorphism which affects the Sb uptake, ultimately leading to drug resistance. Mosaic aneuploidy causes increased copy number variation which leads to chromosomal amplification thus modulating the gene expression in several members of leishmanial parasites for drug resistance.
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