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Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites

Leishmaniasis constitutes the 9(th) largest disease burden among all infectious diseases. Control of this disease is based on a short list of chemotherapeutic agents headed by pentavalent antimonials, followed by miltefosine and amphotericin B; drugs that are far from ideal due to host toxicity, ele...

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Autores principales: Douanne, Noélie, Dong, George, Douanne, Mélanie, Olivier, Martin, Fernandez-Prada, Christopher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365475/
https://www.ncbi.nlm.nih.gov/pubmed/32628683
http://dx.doi.org/10.1371/journal.pntd.0008439
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author Douanne, Noélie
Dong, George
Douanne, Mélanie
Olivier, Martin
Fernandez-Prada, Christopher
author_facet Douanne, Noélie
Dong, George
Douanne, Mélanie
Olivier, Martin
Fernandez-Prada, Christopher
author_sort Douanne, Noélie
collection PubMed
description Leishmaniasis constitutes the 9(th) largest disease burden among all infectious diseases. Control of this disease is based on a short list of chemotherapeutic agents headed by pentavalent antimonials, followed by miltefosine and amphotericin B; drugs that are far from ideal due to host toxicity, elevated cost, limited access, and high rates of drug resistance. Knowing that the composition of extracellular vesicles (EVs) can vary according to the state of their parental cell, we hypothesized that EVs released by drug-resistant Leishmania infantum parasites could contain unique and differently enriched proteins depending on the drug-resistance mechanisms involved in the survival of their parental cell line. To assess this possibility, we studied EV production, size, morphology, and protein content of three well-characterized drug-resistant L. infantum cell lines and a wild-type strain. Our results are the first to demonstrate that drug-resistance mechanisms can induce changes in the morphology, size, and distribution of L. infantum EVs. In addition, we identified L. infantum’s core EV proteome. This proteome is highly conserved among strains, with the exception of a handful of proteins that are enriched differently depending on the drug responsible for induction of antimicrobial resistance. Furthermore, we obtained the first snapshot of proteins enriched in EVs released by antimony-, miltefosine- and amphotericin-resistant parasites. These include several virulence factors, transcription factors, as well as proteins encoded by drug-resistance genes. This detailed study of L. infantum EVs sheds new light on the potential roles of EVs in Leishmania biology, particularly with respect to the parasite’s survival in stressful conditions. This work outlines a crucial first step towards the discovery of EV-based profiles capable of predicting response to antileishmanial agents.
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spelling pubmed-73654752020-07-27 Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites Douanne, Noélie Dong, George Douanne, Mélanie Olivier, Martin Fernandez-Prada, Christopher PLoS Negl Trop Dis Research Article Leishmaniasis constitutes the 9(th) largest disease burden among all infectious diseases. Control of this disease is based on a short list of chemotherapeutic agents headed by pentavalent antimonials, followed by miltefosine and amphotericin B; drugs that are far from ideal due to host toxicity, elevated cost, limited access, and high rates of drug resistance. Knowing that the composition of extracellular vesicles (EVs) can vary according to the state of their parental cell, we hypothesized that EVs released by drug-resistant Leishmania infantum parasites could contain unique and differently enriched proteins depending on the drug-resistance mechanisms involved in the survival of their parental cell line. To assess this possibility, we studied EV production, size, morphology, and protein content of three well-characterized drug-resistant L. infantum cell lines and a wild-type strain. Our results are the first to demonstrate that drug-resistance mechanisms can induce changes in the morphology, size, and distribution of L. infantum EVs. In addition, we identified L. infantum’s core EV proteome. This proteome is highly conserved among strains, with the exception of a handful of proteins that are enriched differently depending on the drug responsible for induction of antimicrobial resistance. Furthermore, we obtained the first snapshot of proteins enriched in EVs released by antimony-, miltefosine- and amphotericin-resistant parasites. These include several virulence factors, transcription factors, as well as proteins encoded by drug-resistance genes. This detailed study of L. infantum EVs sheds new light on the potential roles of EVs in Leishmania biology, particularly with respect to the parasite’s survival in stressful conditions. This work outlines a crucial first step towards the discovery of EV-based profiles capable of predicting response to antileishmanial agents. Public Library of Science 2020-07-06 /pmc/articles/PMC7365475/ /pubmed/32628683 http://dx.doi.org/10.1371/journal.pntd.0008439 Text en © 2020 Douanne et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Douanne, Noélie
Dong, George
Douanne, Mélanie
Olivier, Martin
Fernandez-Prada, Christopher
Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites
title Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites
title_full Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites
title_fullStr Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites
title_full_unstemmed Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites
title_short Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites
title_sort unravelling the proteomic signature of extracellular vesicles released by drug-resistant leishmania infantum parasites
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365475/
https://www.ncbi.nlm.nih.gov/pubmed/32628683
http://dx.doi.org/10.1371/journal.pntd.0008439
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