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The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development

Plasmodium vivax hypnozoites persist in the liver, cause malaria relapse and represent a major challenge to malaria elimination. Our previous transcriptomic study provided a novel molecular framework to enhance our understanding of the hypnozoite biology (Voorberg-van der Wel A, et al., 2017). In th...

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Autores principales: Gupta, Devendra Kumar, Dembele, Laurent, Voorberg-van der Wel, Annemarie, Roma, Guglielmo, Yip, Andy, Chuenchob, Vorada, Kangwanrangsan, Niwat, Ishino, Tomoko, Vaughan, Ashley M, Kappe, Stefan H, Flannery, Erika L, Sattabongkot, Jetsumon, Mikolajczak, Sebastian, Bifani, Pablo, Kocken, Clemens HM, Diagana, Thierry Tidiane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542585/
https://www.ncbi.nlm.nih.gov/pubmed/31094679
http://dx.doi.org/10.7554/eLife.43362
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author Gupta, Devendra Kumar
Dembele, Laurent
Voorberg-van der Wel, Annemarie
Roma, Guglielmo
Yip, Andy
Chuenchob, Vorada
Kangwanrangsan, Niwat
Ishino, Tomoko
Vaughan, Ashley M
Kappe, Stefan H
Flannery, Erika L
Sattabongkot, Jetsumon
Mikolajczak, Sebastian
Bifani, Pablo
Kocken, Clemens HM
Diagana, Thierry Tidiane
author_facet Gupta, Devendra Kumar
Dembele, Laurent
Voorberg-van der Wel, Annemarie
Roma, Guglielmo
Yip, Andy
Chuenchob, Vorada
Kangwanrangsan, Niwat
Ishino, Tomoko
Vaughan, Ashley M
Kappe, Stefan H
Flannery, Erika L
Sattabongkot, Jetsumon
Mikolajczak, Sebastian
Bifani, Pablo
Kocken, Clemens HM
Diagana, Thierry Tidiane
author_sort Gupta, Devendra Kumar
collection PubMed
description Plasmodium vivax hypnozoites persist in the liver, cause malaria relapse and represent a major challenge to malaria elimination. Our previous transcriptomic study provided a novel molecular framework to enhance our understanding of the hypnozoite biology (Voorberg-van der Wel A, et al., 2017). In this dataset, we identified and characterized the Liver-Specific Protein 2 (LISP2) protein as an early molecular marker of liver stage development. Immunofluorescence analysis of hepatocytes infected with relapsing malaria parasites, in vitro (P. cynomolgi) and in vivo (P. vivax), reveals that LISP2 expression discriminates between dormant hypnozoites and early developing parasites. We further demonstrate that prophylactic drugs selectively kill all LISP2-positive parasites, while LISP2-negative hypnozoites are only sensitive to anti-relapse drug tafenoquine. Our results provide novel biological insights in the initiation of liver stage schizogony and an early marker suitable for the development of drug discovery assays predictive of anti-relapse activity.
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spelling pubmed-65425852019-06-12 The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development Gupta, Devendra Kumar Dembele, Laurent Voorberg-van der Wel, Annemarie Roma, Guglielmo Yip, Andy Chuenchob, Vorada Kangwanrangsan, Niwat Ishino, Tomoko Vaughan, Ashley M Kappe, Stefan H Flannery, Erika L Sattabongkot, Jetsumon Mikolajczak, Sebastian Bifani, Pablo Kocken, Clemens HM Diagana, Thierry Tidiane eLife Microbiology and Infectious Disease Plasmodium vivax hypnozoites persist in the liver, cause malaria relapse and represent a major challenge to malaria elimination. Our previous transcriptomic study provided a novel molecular framework to enhance our understanding of the hypnozoite biology (Voorberg-van der Wel A, et al., 2017). In this dataset, we identified and characterized the Liver-Specific Protein 2 (LISP2) protein as an early molecular marker of liver stage development. Immunofluorescence analysis of hepatocytes infected with relapsing malaria parasites, in vitro (P. cynomolgi) and in vivo (P. vivax), reveals that LISP2 expression discriminates between dormant hypnozoites and early developing parasites. We further demonstrate that prophylactic drugs selectively kill all LISP2-positive parasites, while LISP2-negative hypnozoites are only sensitive to anti-relapse drug tafenoquine. Our results provide novel biological insights in the initiation of liver stage schizogony and an early marker suitable for the development of drug discovery assays predictive of anti-relapse activity. eLife Sciences Publications, Ltd 2019-05-16 /pmc/articles/PMC6542585/ /pubmed/31094679 http://dx.doi.org/10.7554/eLife.43362 Text en © 2019, Gupta et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Gupta, Devendra Kumar
Dembele, Laurent
Voorberg-van der Wel, Annemarie
Roma, Guglielmo
Yip, Andy
Chuenchob, Vorada
Kangwanrangsan, Niwat
Ishino, Tomoko
Vaughan, Ashley M
Kappe, Stefan H
Flannery, Erika L
Sattabongkot, Jetsumon
Mikolajczak, Sebastian
Bifani, Pablo
Kocken, Clemens HM
Diagana, Thierry Tidiane
The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development
title The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development
title_full The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development
title_fullStr The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development
title_full_unstemmed The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development
title_short The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development
title_sort plasmodium liver-specific protein 2 (lisp2) is an early marker of liver stage development
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542585/
https://www.ncbi.nlm.nih.gov/pubmed/31094679
http://dx.doi.org/10.7554/eLife.43362
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