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Role of chromatin modulation in the establishment of protozoan parasite infection for developing targeted chemotherapeutics

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Abstract

Four major human infecting protozoan parasites (Plasmodium, Toxoplasma, Leishmania, and Trypanosoma) impose a substantial threat to health and socio-economic status causing significant morbidity and mortality in tropics and subtropics each year. Lack of effective drugs, the emergence of drug-resistance, and toxicity have made the existing treatment regimen insufficient for most of these parasitic infections ranging from acutely lethal to chronic to almost asymptomatic. These pathogens have developed intricate life-cycle stages altering between multiple hosts and initiating a network of developmental processes in response to environmental stimulus for differentiating within the host without evoking host protective immune surveillance. These differentiation events and successful intracellular survival events require drastic and rapid modulation of the parasites and parasite-driven host gene expression which is achieved by substantial chromatin modifications. Histone posttranslational modifications have a marked effect on chromatin structure organization allowing these pathogens to cope with multiple host survival. In this review, we have described the advancements made in interpreting the role of histone modifications and their impact on gene expression throughout the life-cycle stages of these pathogens. Moreover, we have analyzed available genome-wide transcriptomics datasets for each of these pathogens to identify those parasite-specific histone-modifiers which show a preferential expression in human infective stages, with a perspective of anti-parasitic therapies.

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Data availability

The data presented in this review will be made available as per journal policy.

Code availability

All the codes used for analyzing genome-wide transcriptomics data are deposited in GitHub 24 (https://github.com/S1403-pi/Histone-modifiers-of-protozoan-parasites.git).

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Acknowledgements

We would like to acknowledge School of Medical Science and Technology, Indian Institute of Technology, Kharagpur for providing all the infrastructure facilities required for this publication.

Funding

SG is a recipient of IIT-KGP GATE fellowship, S is a recipient of CSIR-NET fellowship. BM 14 lab is funded by SERB and MHRD.

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Authors and Affiliations

  1. School of Medical Science and Technology, IIT Kharagpur, Kharagpur, 721302, India

    Souradeepa Ghosh,  Snehlata, Shahbaj Hussain, Himani Makkar & Budhaditya Mukherjee

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  1. Souradeepa Ghosh
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  2. Snehlata
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  3. Shahbaj Hussain
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  4. Himani Makkar
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  5. Budhaditya Mukherjee
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Contributions

SG participated in preparing the original draft, performed the transcriptome analysis, data preparation, preparing figures, and editing the MS. S participated in preparing the original draft, prepared the figures, and editing the MS. SH performed transcriptome analysis and data preparation. HM participated in preparing and editing the original draft. BM performed supervision, conceptualization, data analyzing, original draft preparation, review, and editing.

Corresponding author

Correspondence to Budhaditya Mukherjee.

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Ghosh, S., Snehlata, Hussain, S. et al. Role of chromatin modulation in the establishment of protozoan parasite infection for developing targeted chemotherapeutics. Nucleus 64, 401–413 (2021). https://doi.org/10.1007/s13237-021-00356-1

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  • DOI: https://doi.org/10.1007/s13237-021-00356-1

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