The Paradigm of Intracellular Parasite Survival and Drug Resistance in Leishmanial Parasite Through Genome Plasticity and Epigenetics: Perception and Future Perspective

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2023 Feb 23

PMID 36814446

Authors

Mohd Kamran

Rahul Bhattacharjee

Sonali Das

Sohitri Mukherjee

Nahid Ali

Affiliations

Soon will be listed here.

Abstract

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 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.

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References

Castellucci L, de Almeida L, Jamieson S, Fakiola M, de Carvalho E, Blackwell J . Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil. Mem Inst Oswaldo Cruz. 2014; 109(3):279-88. PMC: 4131779. DOI: 10.1590/0074-0276140028. View

Uzcategui N, Zhou Y, Figarella K, Ye J, Mukhopadhyay R, Bhattacharjee H . Alteration in glycerol and metalloid permeability by a single mutation in the extracellular C-loop of Leishmania major aquaglyceroporin LmAQP1. Mol Microbiol. 2008; 70(6):1477-86. PMC: 2702841. DOI: 10.1111/j.1365-2958.2008.06494.x. View

Laffitte M, Leprohon P, Legare D, Ouellette M . Deep-sequencing revealing mutation dynamics in the miltefosine transporter gene in Leishmania infantum selected for miltefosine resistance. Parasitol Res. 2016; 115(10):3699-703. DOI: 10.1007/s00436-016-5195-y. View

Reynolds D, Hofmeister B, Cliffe L, Siegel T, Anderson B, Beverley S . Base J represses genes at the end of polycistronic gene clusters in Leishmania major by promoting RNAP II termination. Mol Microbiol. 2016; 101(4):559-74. PMC: 5038137. DOI: 10.1111/mmi.13408. View

Decuypere S, Rijal S, Yardley V, De Doncker S, Laurent T, Khanal B . Gene expression analysis of the mechanism of natural Sb(V) resistance in Leishmania donovani isolates from Nepal. Antimicrob Agents Chemother. 2005; 49(11):4616-21. PMC: 1280167. DOI: 10.1128/AAC.49.11.4616-4621.2005. View

Ivens A, Peacock C, Worthey E, Murphy L, Aggarwal G, Berriman M . The genome of the kinetoplastid parasite, Leishmania major. Science. 2005; 309(5733):436-42. PMC: 1470643. DOI: 10.1126/science.1112680. View

Genois M, Paquet E, Laffitte M, Maity R, Rodrigue A, Ouellette M . DNA repair pathways in trypanosomatids: from DNA repair to drug resistance. Microbiol Mol Biol Rev. 2014; 78(1):40-73. PMC: 3957735. DOI: 10.1128/MMBR.00045-13. View

Musa A, Younis B, Fadlalla A, Royce C, Balasegaram M, Wasunna M . Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. PLoS Negl Trop Dis. 2010; 4(10):e855. PMC: 2964291. DOI: 10.1371/journal.pntd.0000855. View

McCarter L . Regulation of flagella. Curr Opin Microbiol. 2006; 9(2):180-6. DOI: 10.1016/j.mib.2006.02.001. View

10.

Marr A, MacIsaac J, Jiang R, Airo A, Kobor M, McMaster W . Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages. PLoS Pathog. 2014; 10(10):e1004419. PMC: 4192605. DOI: 10.1371/journal.ppat.1004419. View

11.

Azevedo A, Toledo J, Defina T, Pedrosa A, Cruz A . Leishmania major phosphoglycerate kinase transcript and protein stability contributes to differences in isoform expression levels. Exp Parasitol. 2015; 159:222-6. DOI: 10.1016/j.exppara.2015.09.008. View

12.

Wright A, Nunez J, Doudna J . Biology and Applications of CRISPR Systems: Harnessing Nature's Toolbox for Genome Engineering. Cell. 2016; 164(1-2):29-44. DOI: 10.1016/j.cell.2015.12.035. View

13.

Thomas S, Green A, Sturm N, Campbell D, Myler P . Histone acetylations mark origins of polycistronic transcription in Leishmania major. BMC Genomics. 2009; 10:152. PMC: 2679053. DOI: 10.1186/1471-2164-10-152. View

14.

Azizi H, Dumas C, Papadopoulou B . The Pumilio-domain protein PUF6 contributes to SIDER2 retroposon-mediated mRNA decay in . RNA. 2017; 23(12):1874-1885. PMC: 5689007. DOI: 10.1261/rna.062950.117. View

15.

Genois M, Plourde M, Ethier C, Roy G, Poirier G, Ouellette M . Roles of Rad51 paralogs for promoting homologous recombination in Leishmania infantum. Nucleic Acids Res. 2015; 43(5):2701-15. PMC: 4357719. DOI: 10.1093/nar/gkv118. View

16.

Carter N, DREW M, Sanchez M, Vasudevan G, Landfear S, Ullman B . Cloning of a novel inosine-guanosine transporter gene from Leishmania donovani by functional rescue of a transport-deficient mutant. J Biol Chem. 2000; 275(27):20935-41. DOI: 10.1074/jbc.M002418200. View

17.

Roussel M, Nacher M, Fremont G, Rotureau B, Clyti E, Sainte-Marie D . Comparison between one and two injections of pentamidine isethionate, at 7 mg/kg in each injection, in the treatment of cutaneous leishmaniasis in French Guiana. Ann Trop Med Parasitol. 2006; 100(4):307-14. DOI: 10.1179/136485906X105561. View

18.

Ouellette M, Papadopoulou B . Coordinated gene expression by post-transcriptional regulons in African trypanosomes. J Biol. 2009; 8(11):100. PMC: 2804284. DOI: 10.1186/jbiol203. View

19.

Kuhn D, Wiese M . LmxPK4, a mitogen-activated protein kinase kinase homologue of Leishmania mexicana with a potential role in parasite differentiation. Mol Microbiol. 2005; 56(5):1169-82. DOI: 10.1111/j.1365-2958.2005.04614.x. View

20.

Leifso K, Cohen-Freue G, Dogra N, Murray A, McMaster W . Genomic and proteomic expression analysis of Leishmania promastigote and amastigote life stages: the Leishmania genome is constitutively expressed. Mol Biochem Parasitol. 2006; 152(1):35-46. DOI: 10.1016/j.molbiopara.2006.11.009. View