The malarial serine protease SUB1 plays an essential role in parasite liver stage development.

Transmission of the malaria parasite to its vertebrate host involves an obligatory exoerythrocytic stage in which extensive asexual replication of the parasite takes place in infected hepatocytes. The resulting liver schizont undergoes segmentation to produce thousands of daughter merozoites. These...

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Autores principales:	Catherine Suarez, Katrin Volkmann, Ana Rita Gomes, Oliver Billker, Michael J Blackman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d6bf097e500c42f9867b762c3bacdeb4
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spelling	oai:doaj.org-article:d6bf097e500c42f9867b762c3bacdeb42021-11-18T06:07:14ZThe malarial serine protease SUB1 plays an essential role in parasite liver stage development.1553-73661553-737410.1371/journal.ppat.1003811https://doaj.org/article/d6bf097e500c42f9867b762c3bacdeb42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24348254/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Transmission of the malaria parasite to its vertebrate host involves an obligatory exoerythrocytic stage in which extensive asexual replication of the parasite takes place in infected hepatocytes. The resulting liver schizont undergoes segmentation to produce thousands of daughter merozoites. These are released to initiate the blood stage life cycle, which causes all the pathology associated with the disease. Whilst elements of liver stage merozoite biology are similar to those in the much better-studied blood stage merozoites, little is known of the molecular players involved in liver stage merozoite production. To facilitate the study of liver stage biology we developed a strategy for the rapid production of complex conditional alleles by recombinase mediated engineering in Escherichia coli, which we used in combination with existing Plasmodium berghei deleter lines expressing Flp recombinase to study subtilisin-like protease 1 (SUB1), a conserved Plasmodium serine protease previously implicated in blood stage merozoite maturation and egress. We demonstrate that SUB1 is not required for the early stages of intrahepatic growth, but is essential for complete development of the liver stage schizont and for production of hepatic merozoites. Our results indicate that inhibitors of SUB1 could be used in prophylactic approaches to control or block the clinically silent pre-erythrocytic stage of the malaria parasite life cycle.Catherine SuarezKatrin VolkmannAna Rita GomesOliver BillkerMichael J BlackmanPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 12, p e1003811 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Catherine Suarez Katrin Volkmann Ana Rita Gomes Oliver Billker Michael J Blackman The malarial serine protease SUB1 plays an essential role in parasite liver stage development.
description	Transmission of the malaria parasite to its vertebrate host involves an obligatory exoerythrocytic stage in which extensive asexual replication of the parasite takes place in infected hepatocytes. The resulting liver schizont undergoes segmentation to produce thousands of daughter merozoites. These are released to initiate the blood stage life cycle, which causes all the pathology associated with the disease. Whilst elements of liver stage merozoite biology are similar to those in the much better-studied blood stage merozoites, little is known of the molecular players involved in liver stage merozoite production. To facilitate the study of liver stage biology we developed a strategy for the rapid production of complex conditional alleles by recombinase mediated engineering in Escherichia coli, which we used in combination with existing Plasmodium berghei deleter lines expressing Flp recombinase to study subtilisin-like protease 1 (SUB1), a conserved Plasmodium serine protease previously implicated in blood stage merozoite maturation and egress. We demonstrate that SUB1 is not required for the early stages of intrahepatic growth, but is essential for complete development of the liver stage schizont and for production of hepatic merozoites. Our results indicate that inhibitors of SUB1 could be used in prophylactic approaches to control or block the clinically silent pre-erythrocytic stage of the malaria parasite life cycle.
format	article
author	Catherine Suarez Katrin Volkmann Ana Rita Gomes Oliver Billker Michael J Blackman
author_facet	Catherine Suarez Katrin Volkmann Ana Rita Gomes Oliver Billker Michael J Blackman
author_sort	Catherine Suarez
title	The malarial serine protease SUB1 plays an essential role in parasite liver stage development.
title_short	The malarial serine protease SUB1 plays an essential role in parasite liver stage development.
title_full	The malarial serine protease SUB1 plays an essential role in parasite liver stage development.
title_fullStr	The malarial serine protease SUB1 plays an essential role in parasite liver stage development.
title_full_unstemmed	The malarial serine protease SUB1 plays an essential role in parasite liver stage development.
title_sort	malarial serine protease sub1 plays an essential role in parasite liver stage development.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d6bf097e500c42f9867b762c3bacdeb4
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The malarial serine protease SUB1 plays an essential role in parasite liver stage development.

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