Trypanosomatids see the light: recent advances in bioimaging research

Calvo-Álvarez, Estefanía; Álvarez-Velilla, Raquel; Fernández-Prada, Christopher; Balaña‐Fouce, Rafael; Reguera, Rosa M.

doi:10.1016/j.drudis.2014.09.012

Cited by 14 publications

(16 citation statements)

References 68 publications

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“…Despite the fact that our results showed a decrease in the antiparasitic effect after DOX conjugation, the EC 50 values obtained are in the micromolar order similar to those obtained by others. This opposite effect can be attributed to either the leishmania species used in the experiments ( L. infantum vs Leishmania donovani ), or to a higher drug sensitivity in our ex vivo splenic explant than that provided by infected J774A.1 macrophages. Collectively, our results show a SI value for free DOX < 1 (Figure C CC 50 /Figure B EC 50 (0.28/0.43)), which is not surprising given that J774A.1 is a tumoral cell line that is used as macrophage model for testing leishmania infection.…”

Section: Resultsmentioning

confidence: 87%

PEGylated Dendritic Polyglycerol Conjugate Delivers Doxorubicin to the Parasitophorous Vacuole in Leishmania infantum Infections

Gutiérrez-Corbo

Domínguez-Asenjo

Vossen

et al. 2017

Macromolecular Bioscience

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Most drugs against visceral leishmaniasis must be administered parenterally. A controlled drug release at the target site can improve the efficacy and toxicity of antileishmanial drugs in clinical use. Amastigotes live and grow inside the parasitophorous vacuole of host resident macrophages. Therefore, antileishmanial drugs should accumulate in this compartment to kill the parasite and do not produce toxicity to the cell host. PEGylated dendritic polyglycerol conjugates (PG‐PEG) can ensure a controlled drug release and the immune activation efficiency of the host. A dendritic PG conjugate with doxorubicin (DOX) attached through a pH‐cleavable hydrazone linker (PG‐DOX(pH)‐PEG), is tested on murine macrophage cell lines and on ex vivo infected BALB/c splenocytes. As a control, a dendritic PG conjugate attached via a non‐cleavable linker (PG‐DOX(non)‐PEG) is used. DOX fluorescence is useful to monitor the fate of the drug inside the infected cells by flow cytometry and confocal microscopy. The results show that PG‐DOX(pH)‐PEG slowly releases DOX inside the targeted macrophages, protecting the host of toxic drug concentrations. In addition, unlike free DOX, PG‐DOX(pH)‐PEG is actively internalized through the acidic endocytic pathway and colocalized surrounding the amastigotes. These results prove that PG‐DOX(pH)‐PEG is a promising candidate for releasing antileishmanial drugs in a controlled manner.

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Section: Resultsmentioning

confidence: 87%

PEGylated Dendritic Polyglycerol Conjugate Delivers Doxorubicin to the Parasitophorous Vacuole in Leishmania infantum Infections

Gutiérrez-Corbo

Domínguez-Asenjo

Vossen

et al. 2017

Macromolecular Bioscience

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“…In the context of diagnostic tool and drug development, as well as in order to study the complex developmental cycles of trypanosomatid parasites, genetically engineered parasites have been developed to express a large panel of molecular reporters including fluorescent and bioluminescent probes both in T. cruzi (Lewis et al, 2015) and T. brucei (Burrell-Saward et al, 2015;Coles et al, 2017;MacLean et al, 2013;McLatchie et al, 2013;Van Reet et al, 2014), and especially in Leishmania spp. (Beattie and Kaye, 2011;Calvo-Alvarez et al, 2015a;Carneiro et al, 2017;Forestier, 2013;Lang et al, 2009;Taheri et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

A new chimeric triple reporter fusion protein as a tool for in vitro and in vivo multimodal imaging to monitor the development of African trypanosomes and Leishmania parasites

Calvo-Álvarez

Travaillé

Crouzols

et al. 2018

Infection, Genetics and Evolution

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“…For instance, the firefly luciferase gene is widely used as a reporter gene in gene expression analysis ( De Wet et al, 1985 ; Koncz et al, 1990 ). Firefly luciferases have been used in different applications, e.g., bioimaging ( Calvo-Álvarez et al, 2015 ; Reimão et al, 2015 ), protein-protein interaction assay ( Kurihara et al, 2016 ), immunoassay ( Smirnova, Samsonova & Ugarova, 2016 ), and ATP quantification ( Marques & Esteves da Silva, 2009 ). However, knowledge about the biosynthesis of the luciferase substrate, luciferin, is still lacking.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis reveals candidate genes involved in luciferin metabolism inLuciola aquatilis(Coleoptera: Lampyridae)

Vongsangnak

Chumnanpuen

Sriboonlert

2016

PeerJ

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Bioluminescence, which living organisms such as fireflies emit light, has been studied extensively for over half a century. This intriguing reaction, having its origins in nature where glowing insects can signal things such as attraction or defense, is now widely used in biotechnology with applications of bioluminescence and chemiluminescence. Luciferase, a key enzyme in this reaction, has been well characterized; however, the enzymes involved in the biosynthetic pathway of its substrate, luciferin, remains unsolved at present. To elucidate the luciferin metabolism, we performed a de novo transcriptome analysis using larvae of the firefly species, Luciola aquatilis. Here, a comparative analysis is performed with the model coleopteran insect Tribolium casteneum to elucidate the metabolic pathways in L. aquatilis. Based on a template luciferin biosynthetic pathway, combined with a range of protein and pathway databases, and various prediction tools for functional annotation, the candidate genes, enzymes, and biochemical reactions involved in luciferin metabolism are proposed for L. aquatilis. The candidate gene expression is validated in the adult L. aquatilis using reverse transcription PCR (RT-PCR). This study provides useful information on the bio-production of luciferin in the firefly and will benefit to future applications of the valuable firefly bioluminescence system.

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Trypanosomatids see the light: recent advances in bioimaging research

Cited by 14 publications

References 68 publications

PEGylated Dendritic Polyglycerol Conjugate Delivers Doxorubicin to the Parasitophorous Vacuole in Leishmania infantum Infections

PEGylated Dendritic Polyglycerol Conjugate Delivers Doxorubicin to the Parasitophorous Vacuole in Leishmania infantum Infections

A new chimeric triple reporter fusion protein as a tool for in vitro and in vivo multimodal imaging to monitor the development of African trypanosomes and Leishmania parasites

Transcriptome analysis reveals candidate genes involved in luciferin metabolism inLuciola aquatilis(Coleoptera: Lampyridae)

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