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The Malarial Serine Protease SUB1 Plays an Essential Role in Parasite Liver Stage Development
Wellcome Trust Sanger Institute, Hinxton,Cambridge, United Kingdom.ORCID iD: 0000-0003-1716-168x
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2013 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 9, no 12, article id e1003811Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Public Library of Science , 2013. Vol. 9, no 12, article id e1003811
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Cell and Molecular Biology
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URN: urn:nbn:se:umu:diva-165860DOI: 10.1371/journal.ppat.1003811ISI: 000330535400042PubMedID: 24348254Scopus ID: 2-s2.0-84892896712OAI: oai:DiVA.org:umu-165860DiVA, id: diva2:1379364
Available from: 2019-12-17 Created: 2019-12-17 Last updated: 2019-12-20Bibliographically approved

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