A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609

Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite–infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent t...

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Detalles Bibliográficos
Autores principales: Zhang, Rou, Suwanarusk, Rossarin, Malleret, Benoit, Cooke, Brian M., Nosten, Francois, Lau, Yee-Ling, Dao, Ming, Lim, Chwee Teck, Renia, Laurent, Tan, Kevin Shyong Wei, Russell, Bruce
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Major Articles and Brief Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676544/
https://www.ncbi.nlm.nih.gov/pubmed/26136472
http://dx.doi.org/10.1093/infdis/jiv358
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author Zhang, Rou
Suwanarusk, Rossarin
Malleret, Benoit
Cooke, Brian M.
Nosten, Francois
Lau, Yee-Ling
Dao, Ming
Lim, Chwee Teck
Renia, Laurent
Tan, Kevin Shyong Wei
Russell, Bruce
author_facet Zhang, Rou
Suwanarusk, Rossarin
Malleret, Benoit
Cooke, Brian M.
Nosten, Francois
Lau, Yee-Ling
Dao, Ming
Lim, Chwee Teck
Renia, Laurent
Tan, Kevin Shyong Wei
Russell, Bruce
author_sort Zhang, Rou
collection PubMed
description Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite–infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax– and Plasmodium falciparum–infected RBCs.
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spelling pubmed-46765442016-01-08 A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609 Zhang, Rou Suwanarusk, Rossarin Malleret, Benoit Cooke, Brian M. Nosten, Francois Lau, Yee-Ling Dao, Ming Lim, Chwee Teck Renia, Laurent Tan, Kevin Shyong Wei Russell, Bruce J Infect Dis Major Articles and Brief Reports Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite–infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax– and Plasmodium falciparum–infected RBCs. Oxford University Press 2016-01-01 2015-07-01 /pmc/articles/PMC4676544/ /pubmed/26136472 http://dx.doi.org/10.1093/infdis/jiv358 Text en © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Major Articles and Brief Reports
Zhang, Rou
Suwanarusk, Rossarin
Malleret, Benoit
Cooke, Brian M.
Nosten, Francois
Lau, Yee-Ling
Dao, Ming
Lim, Chwee Teck
Renia, Laurent
Tan, Kevin Shyong Wei
Russell, Bruce
A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609
title A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609
title_full A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609
title_fullStr A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609
title_full_unstemmed A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609
title_short A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609
title_sort basis for rapid clearance of circulating ring-stage malaria parasites by the spiroindolone kae609
topic Major Articles and Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676544/
https://www.ncbi.nlm.nih.gov/pubmed/26136472
http://dx.doi.org/10.1093/infdis/jiv358
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