Leishmania tarentolae for the Production of Multi-subunit Complexes

Niimi, Tomoaki

doi:10.1007/978-3-319-27216-0_10

Cited by 7 publications

(5 citation statements)

References 64 publications

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“…L . tarentolae is a non-pathogenic parasite that does not cause pathology in humans nor in immunodeficient mice and its non-pathogenicity has been recently proven in several studies [ 55 , 64 , 65 ]. We showed here that injection of L .…”

Section: Discussionmentioning

confidence: 99%

Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites

et al. 2017

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Proliferation of Leishmania (L.) parasites depends on polyamine availability, which can be generated by the L-arginine catabolism and the enzymatic activity of arginase (ARG) of the parasites and of the mammalian hosts. In the present study, we characterized and compared the arginase (arg) genes from pathogenic L. major and L. tropica and from non-pathogenic L. tarentolae. We quantified the level of the ARG activity in promastigotes and macrophages infected with pathogenic L. major and L. tropica and non-pathogenic L. tarentolae amastigotes. The ARG's amino acid sequences of the pathogenic and non-pathogenic Leishmania demonstrated virtually 98.6% and 88% identities with the reference L. major Friedlin ARG. Higher ARG activity was observed in all pathogenic promastigotes as compared to non-pathogenic L. tarentolae. In vitro infection of human macrophage cell line (THP1) with pathogenic and non-pathogenic Leishmania spp. resulted in increased ARG activities in the infected macrophages. The ARG activities present in vivo were assessed in susceptible BALB/c and resistant C57BL/6 mice infected with L. major, L. tropica and L. tarentolae. We demonstrated that during the development of the infection, ARG is induced in both strains of mice infected with pathogenic Leishmania. However, in L. major infected BALB/c mice, the induction of ARG and parasite load increased simultaneously according to the time course of infection, whereas in C57BL/6 mice, the enzyme is upregulated solely during the period of footpad swelling. In L. tropica infected mice, the footpads' swellings were slow to develop and demonstrated minimal cutaneous pathology and ARG activity. In contrast, ARG activity was undetectable in mice inoculated with the non-pathogenic L. tarentolae. Our data suggest that infection by Leishmania parasites can increase ARG activity of the host and provides essential polyamines for parasite salvage and its replication. Moreover, the ARG of Leishmania is vital for parasite proliferation and required for infection in mice. ARG activity can be used as one of the main marker of the disease severity.

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Section: Discussionmentioning

confidence: 99%

Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites

et al. 2017

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“…However, functional expression results of single-chain fragment variables (scFv’s) [12] and scFv-fragment crystallizable (scFv-Fc) fusion proteins [13] indicate that successful expression of full-length antibodies is only a matter of time [130]. The successful expression of multisubunit proteins, like the human heterotrimeric glycoprotein LM-322 [17,131], further underpins the general capacity of L . tarentolae to express full-length antibodies, as they also consist of several subunits.…”

Section: Biotechnological Applications Of L Tarentolaementioning

confidence: 99%

Leishmania tarentolae: Taxonomic classification and its application as a promising biotechnological expression host

et al. 2019

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In this review, we summarize the current knowledge concerning the eukaryotic protozoan parasite Leishmania tarentolae , with a main focus on its potential for biotechnological applications. We will also discuss the genus, subgenus, and species-level classification of this parasite, its life cycle and geographical distribution, and similarities and differences to human-pathogenic species, as these aspects are relevant for the evaluation of biosafety aspects of L . tarentolae as host for recombinant DNA/protein applications. Studies indicate that strain LEM-125 but not strain TARII/UC of L . tarentolae might also be capable of infecting mammals, at least transiently. This could raise the question of whether the current biosafety level of this strain should be reevaluated. In addition, we will summarize the current state of biotechnological research involving L . tarentolae and explain why this eukaryotic parasite is an advantageous and promising human recombinant protein expression host. This summary includes overall biotechnological applications, insights into its protein expression machinery (especially on glycoprotein and antibody fragment expression), available expression vectors, cell culture conditions, and its potential as an immunotherapy agent for human leishmaniasis treatment. Furthermore, we will highlight useful online tools and, finally, discuss possible future applications such as the humanization of the glycosylation profile of L . tarentolae or the expression of mammalian recombinant proteins in amastigote-like cells of this species or in amastigotes of avirulent human-pathogenic Leishmania species.

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“…The protozoan parasites of the genus Leishmania belong to the Trypanosomatidae family (one of the oldest groups of eukaryotes), which comprises unicellular organisms recognized by their single flagellum and a unique mitochondrial DNA-containing organelle, the kinetoplast ( Niimi, 2016 ). Due to its public health significance, the Trypanosomatidae group is one of the best-studied eukaryotic groups after yeast ( Basile and Peticca, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

“…L. tarentolae does not cause pathogenicity in humans and even in severe combined immunodeficient mice (Breton et al, 2005;Niimi, 2016). Recently, many studies on animals, such as mice, hamsters, and dogs have shown that the use of L. tarentolae can be a promising approach for vaccine development (as a live vector) against CL and VL (Saljoughian et al, 2013;Zahedifard et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…L. tarentolae can infect macrophages and dendritic cells, but its survival and propagation in mammalian cells are limited (Breton et al, 2005). Furthermore, L. tarentolae can act as an efficient delivery system due to its unique features that have the ability to produce mammalian-like complex N-glycosylation patterns, the ease of genetic manipulation, the straightforward adaptation to large-scale production, the minimal nutrition requirements, and, most importantly, the ability to target dendritic cells and secondary lymphoid organs and to create Th1 responses and IFN-g production (Basile and Peticca, 2009;Mizbani et al, 2009;Bolhassani et al, 2011;Saljoughian et al, 2013;Zahedifard et al, 2014;Katebi et al, 2015;Niimi, 2016;Abdossamadi et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Isolation, characterization, and functional study of extracellular vesicles derived from Leishmania tarentolae

Shokouhy

Sarvnaz

Taslimi

et al. 2022

Front. Cell. Infect. Microbiol.

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Leishmania (L.) species are protozoan parasites with a complex life cycle consisting of a number of developmental forms that alternate between the sand fly vector and their host. The non-pathogenic species L. tarentolae is not able to induce an active infection in a human host. It has been observed that, in pathogenic species, extracellular vesicles (EVs) could exacerbate the infection. However, so far, there is no report on the identification, isolation, and characterization of L. tarentolae EVs. In this study, we have isolated and characterized EVs from L. tarentolaeGFP+ (tEVs) along with L. majorGFP+ as a reference and positive control. The EVs secreted by these two species demonstrated similar particle size distribution (approximately 200 nm) in scanning electron microscopy and nanoparticle tracking analysis. Moreover, the said EVs showed similar protein content, and GFP and GP63 proteins were detected in both using dot blot analysis. Furthermore, we could detect Leishmania-derived GP63 protein in THP-1 cells treated with tEVs. Interestingly, we observed a significant increase in the production of IFN-γ, TNF-α, and IL-1β, while there were no significant differences in IL-6 levels in THP-1 cells treated with tEVs following an infection with L. major compared with another group of macrophages that were treated with L. major EVs prior to the infection. Another exciting observation of this study was a significant decrease in parasite load in tEV-treated Leishmania-infected macrophages. In addition, in comparison with another group of Leishmania-infected macrophages which was not exposed to any EVs, tEV managed to increase IFN-γ and decrease IL-6 and the parasite burden. In conclusion, we report for the first time that L. tarentolae can release EVs and provide evidence that tEVs are able to control the infection in human macrophages, making them a great potential platform for drug delivery, at least for parasitic infections.

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Leishmania tarentolae for the Production of Multi-subunit Complexes

Cited by 7 publications

References 64 publications

Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites

Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites

Leishmania tarentolae: Taxonomic classification and its application as a promising biotechnological expression host

Isolation, characterization, and functional study of extracellular vesicles derived from Leishmania tarentolae

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