Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites.
Leishmaniasis constitutes the 9th 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, eleva...
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ftdoajarticles:oai:doaj.org/article:fa9634a1a10f4ed2a137b46b9f7c207f 2023-05-15T15:13:25+02:00 Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites. Noélie Douanne George Dong Mélanie Douanne Martin Olivier Christopher Fernandez-Prada 2020-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008439 https://doaj.org/article/fa9634a1a10f4ed2a137b46b9f7c207f EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008439 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008439 https://doaj.org/article/fa9634a1a10f4ed2a137b46b9f7c207f PLoS Neglected Tropical Diseases, Vol 14, Iss 7, p e0008439 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008439 2022-12-31T07:56:47Z Leishmaniasis constitutes the 9th 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 7 e0008439 |
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Directory of Open Access Journals: DOAJ Articles |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Noélie Douanne George Dong Mélanie Douanne Martin Olivier Christopher Fernandez-Prada Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Leishmaniasis constitutes the 9th 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. |
format |
Article in Journal/Newspaper |
author |
Noélie Douanne George Dong Mélanie Douanne Martin Olivier Christopher Fernandez-Prada |
author_facet |
Noélie Douanne George Dong Mélanie Douanne Martin Olivier Christopher Fernandez-Prada |
author_sort |
Noélie Douanne |
title |
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_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_sort |
unravelling the proteomic signature of extracellular vesicles released by drug-resistant leishmania infantum parasites. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008439 https://doaj.org/article/fa9634a1a10f4ed2a137b46b9f7c207f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 7, p e0008439 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008439 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008439 https://doaj.org/article/fa9634a1a10f4ed2a137b46b9f7c207f |
op_doi |
https://doi.org/10.1371/journal.pntd.0008439 |
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PLOS Neglected Tropical Diseases |
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14 |
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7 |
container_start_page |
e0008439 |
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1766343967510626304 |