Leishmania guyanensis M4147 as a new LRV1-bearing model parasite: Phosphatidate phosphatase 2-like protein controls cell cycle progression and intracellular lipid content

Abstract

Leishmaniasis is a parasitic vector-borne disease caused by the protistan flagellates of the genus Leishmania. Leishmania (Viannia) guyanensis is one of the most common causative agents of the American tegumentary leishmaniasis. It has previously been shown that L. guyanensis strains that carry the endosymbiotic Leishmania RNA virus 1 (LRV1) cause more severe form of the disease in a mouse model than those that do not. The presence of the virus was implicated into the parasite’s replication and spreading. In this respect, studying the molecular mechanisms of cellular control of viral infection is of great medical importance. Here, we report ~30.5 Mb high-quality genome assembly of the LRV1-positive L. guyanensis M4147. This strain was turned into a model by establishing the CRISPR-Cas9 system and ablating the gene encoding phosphatidate phosphatase 2-like (PAP2L) protein. The orthologue of this gene is conspicuously absent from the genome of an unusual member of the family Trypanosomatidae, Vickermania ingenoplastis, a species with mostly bi-flagellated cells. Our analysis of the PAP2L-null L. guyanensis showed an increase in the number of cells strikingly resembling the bi-flagellated V. ingenoplastis, likely as a result of the disruption of the cell cycle, significant accumulation of phosphatidic acid, and increased virulence compared to the wild type cells.

Revisiting epidemiology of leishmaniasis in central Asia: lessons learnt

“…discussed above have been sequenced. The iconic one, L. major MHOM/IL/81/Friedlin had been sequenced earlier in 2005 (Ivens et al ., 2005 ) and since then was used as a reference in numerous comparative studies (El-Sayed et al ., 2005 ; Peacock et al ., 2007 ; Lukeš et al ., 2018 ; Zakharova et al ., 2022 ). The genomes of L. turanica MRHO/SU/65/VL (LEM423) and L. gerbilli MRHO/CN/60/GERBILLI (LEM452) are also available, but they have not been scrupulously analysed yet (Warren et al ., 2021 ).…”

Elimination of LRVs Elicits Different Responses in Leishmania spp.

“…3A ). Also, a reduced expression of the membrane-bound acid phosphatase 2 ( Table S1 ) is noteworthy, as we have recently demonstrated ablation of a related enzyme (phosphatidate phosphatase 2-like protein) has profound effect in Leishmania biology ( 37 ).…”

“…We employed the standard pLEXSY-based conventional approach to integrate genes encoding LRV1 capsid or its derivatives (Cap-23 and Cap-105) into the 18S rRNA locus of this species as in Zakharova et al and Ishemgulova et al ( 37 , 38 ) ( Fig. 1A ).…”

TriTrypDB: An integrated functional genomics resource for kinetoplastida

“…Below are a few recent examples of how TriTrypDB data and tools have been utilized by the research community to conduct their own research. TriTrypDB genomes and annotations have been used to characterize individual genes [69][70][71][72][73] or gene families [74,75], identify orthologs across species [55,70,76], conduct genome-wide analyses to study genetic variations such as SNPs, CNVs and hybridization events [77][78][79], perform comparative genomic [80][81][82] and phylogenetic/ phylogenomic [82,83] analyses, and as reference genomes for the assembly and/or annotation of newly generated genomes [16,84]. Similarly, the genome assemblies and annotations have also been utilized for the analysis of differential gene expression [19,72,85], protein expression [85][86][87], the identification of post-translational modifications [72] and potential new genes missing in the official gene sets [88].…”