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A Plasmodium cysteine protease required for efficient transition from the liver infection stage
The transitions between developmental stages are critical points in the Plasmodium life cycle. The development of Plasmodium in the livers of their mammalian hosts bridges malaria transmission and the onset of clinical symptoms elicited by red blood cell infection. The egress of Plasmodium parasites...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529260/ https://www.ncbi.nlm.nih.gov/pubmed/32956401 http://dx.doi.org/10.1371/journal.ppat.1008891 |
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author | Putrianti, Elyzana Dewi Schmidt-Christensen, Anja Heussler, Volker Matuschewski, Kai Ingmundson, Alyssa |
author_facet | Putrianti, Elyzana Dewi Schmidt-Christensen, Anja Heussler, Volker Matuschewski, Kai Ingmundson, Alyssa |
author_sort | Putrianti, Elyzana Dewi |
collection | PubMed |
description | The transitions between developmental stages are critical points in the Plasmodium life cycle. The development of Plasmodium in the livers of their mammalian hosts bridges malaria transmission and the onset of clinical symptoms elicited by red blood cell infection. The egress of Plasmodium parasites from the liver must be a carefully orchestrated process to ensure a successful switch to the blood stage of infection. Cysteine protease activity is known to be required for liver-stage Plasmodium egress, but the crucial cysteine protease(s) remained unidentified. Here, we characterize a member of the papain-like cysteine protease family, Plasmodium berghei serine repeat antigen 4 (PbSERA4), that is required for efficient initiation of blood-stage infection. Through the generation PbSERA4-specific antisera and the creation of transgenic parasites expressing fluorescently tagged protein, we show that PbSERA4 is expressed and proteolytically processed in the liver and blood stages of infection. Targeted disruption of PbSERA4 results in viable and virulent blood-stage parasites. However, upon transmission from mosquitoes to mice, Pbsera4(-) parasites displayed a reduced capacity to initiate a new round of asexual blood-stage replication. Our results from cultured cells indicate that this defect results from an inability of the PbSERA4-deficient parasites to egress efficiently from infected cells at the culmination of liver-stage development. Protection against infection with wildtype P. berghei could be generated in animals in which Pbsera4(-) parasites failed to establish infection. Our findings confirm that liver-stage merozoite release is an active process and demonstrate that this parasite-encoded cysteine protease contributes to parasite escape from the liver. |
format | Online Article Text |
id | pubmed-7529260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-75292602020-10-02 A Plasmodium cysteine protease required for efficient transition from the liver infection stage Putrianti, Elyzana Dewi Schmidt-Christensen, Anja Heussler, Volker Matuschewski, Kai Ingmundson, Alyssa PLoS Pathog Research Article The transitions between developmental stages are critical points in the Plasmodium life cycle. The development of Plasmodium in the livers of their mammalian hosts bridges malaria transmission and the onset of clinical symptoms elicited by red blood cell infection. The egress of Plasmodium parasites from the liver must be a carefully orchestrated process to ensure a successful switch to the blood stage of infection. Cysteine protease activity is known to be required for liver-stage Plasmodium egress, but the crucial cysteine protease(s) remained unidentified. Here, we characterize a member of the papain-like cysteine protease family, Plasmodium berghei serine repeat antigen 4 (PbSERA4), that is required for efficient initiation of blood-stage infection. Through the generation PbSERA4-specific antisera and the creation of transgenic parasites expressing fluorescently tagged protein, we show that PbSERA4 is expressed and proteolytically processed in the liver and blood stages of infection. Targeted disruption of PbSERA4 results in viable and virulent blood-stage parasites. However, upon transmission from mosquitoes to mice, Pbsera4(-) parasites displayed a reduced capacity to initiate a new round of asexual blood-stage replication. Our results from cultured cells indicate that this defect results from an inability of the PbSERA4-deficient parasites to egress efficiently from infected cells at the culmination of liver-stage development. Protection against infection with wildtype P. berghei could be generated in animals in which Pbsera4(-) parasites failed to establish infection. Our findings confirm that liver-stage merozoite release is an active process and demonstrate that this parasite-encoded cysteine protease contributes to parasite escape from the liver. Public Library of Science 2020-09-21 /pmc/articles/PMC7529260/ /pubmed/32956401 http://dx.doi.org/10.1371/journal.ppat.1008891 Text en © 2020 Putrianti et al 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 use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Putrianti, Elyzana Dewi Schmidt-Christensen, Anja Heussler, Volker Matuschewski, Kai Ingmundson, Alyssa A Plasmodium cysteine protease required for efficient transition from the liver infection stage |
title | A Plasmodium cysteine protease required for efficient transition from the liver infection stage |
title_full | A Plasmodium cysteine protease required for efficient transition from the liver infection stage |
title_fullStr | A Plasmodium cysteine protease required for efficient transition from the liver infection stage |
title_full_unstemmed | A Plasmodium cysteine protease required for efficient transition from the liver infection stage |
title_short | A Plasmodium cysteine protease required for efficient transition from the liver infection stage |
title_sort | plasmodium cysteine protease required for efficient transition from the liver infection stage |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529260/ https://www.ncbi.nlm.nih.gov/pubmed/32956401 http://dx.doi.org/10.1371/journal.ppat.1008891 |
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