Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites
| Main Author: | |
|---|---|
| Publication Date: | 2017 |
| Other Authors: | , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| Download full: | http://hdl.handle.net/10451/33661 |
Summary: | :© 2017 Hopp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| id |
RCAP_63d00e61f9af208e6ca2a7d0b791776d |
|---|---|
| oai_identifier_str |
oai:repositorio.ulisboa.pt:10451/33661 |
| network_acronym_str |
RCAP |
| network_name_str |
Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| repository_id_str |
https://opendoar.ac.uk/repository/7160 |
| spelling |
Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites:© 2017 Hopp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Proteases have been implicated in a variety of developmental processes during the malaria parasite lifecycle. In particular, invasion and egress of the parasite from the infected hepatocyte and erythrocyte, critically depend on protease activity. Although falcipain-1 was the first cysteine protease to be characterized in P. falciparum, its role in the lifecycle of the parasite has been the subject of some controversy. While an inhibitor of falcipain-1 blocked erythrocyte invasion by merozoites, two independent studies showed that falcipain-1 disruption did not affect growth of blood stage parasites. To shed light on the role of this protease over the entire Plasmodium lifecycle, we disrupted berghepain-1, its ortholog in the rodent parasite P. berghei. We found that this mutant parasite displays a pronounced delay in blood stage infection after inoculation of sporozoites. Experiments designed to pinpoint the defect of berghepain-1 knockout parasites found that it was not due to alterations in gliding motility, hepatocyte invasion or liver stage development and that injection of berghepain-1 knockout merosomes replicated the phenotype of delayed blood stage growth after sporozoite inoculation. We identified an additional role for berghepain-1 in preparing blood stage merozoites for infection of erythrocytes and observed that berghepain-1 knockout parasites exhibit a reticulocyte restriction, suggesting that berghepain-1 activity broadens the erythrocyte repertoire of the parasite. The lack of berghepain-1 expression resulted in a greater reduction in erythrocyte infectivity in hepatocyte-derived merozoites than it did in erythrocyte-derived merozoites. These observations indicate a role for berghepain-1 in processing ligands important for merozoite infectivity and provide evidence supporting the notion that hepatic and erythrocytic merozoites, though structurally similar, are not identical.This work was supported by the National Institutes of Health (R01 grant A1056840 to PS), a Johns Hopkins Malaria Research Institute fellowship (CSH) (malaria.jhsph.edu/opportunities/fellowships/) and the Netherlands Organization for Scientific Research Rubicon fellowship (WAvdL) (www.nwo.nl/funding-rubicon).Public Library of ScienceRepositório da Universidade de LisboaHopp, Christine S.Bennett, Brandy L.Mishra, SatishLehmann, ChristineHanson, Kirsten K.Lin, Jing-wenRousseau, KimberlyCarvalho, Filomena A.van der Linden, Wouter A.Santos, Nuno C.Bogyo, MatthewKhan, Shahid M.Heussler, VolkerSinnis, Photini2018-05-25T14:50:55Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/33661engPLOS Pathogens, 2017, September 18, 2017, e10065861553-736610.1371/journal.ppat.1006586info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T13:54:52Zoai:repositorio.ulisboa.pt:10451/33661Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T02:57:50.524068Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
| dc.title.none.fl_str_mv |
Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites |
| title |
Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites |
| spellingShingle |
Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites Hopp, Christine S. |
| title_short |
Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites |
| title_full |
Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites |
| title_fullStr |
Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites |
| title_full_unstemmed |
Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites |
| title_sort |
Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites |
| author |
Hopp, Christine S. |
| author_facet |
Hopp, Christine S. Bennett, Brandy L. Mishra, Satish Lehmann, Christine Hanson, Kirsten K. Lin, Jing-wen Rousseau, Kimberly Carvalho, Filomena A. van der Linden, Wouter A. Santos, Nuno C. Bogyo, Matthew Khan, Shahid M. Heussler, Volker Sinnis, Photini |
| author_role |
author |
| author2 |
Bennett, Brandy L. Mishra, Satish Lehmann, Christine Hanson, Kirsten K. Lin, Jing-wen Rousseau, Kimberly Carvalho, Filomena A. van der Linden, Wouter A. Santos, Nuno C. Bogyo, Matthew Khan, Shahid M. Heussler, Volker Sinnis, Photini |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Hopp, Christine S. Bennett, Brandy L. Mishra, Satish Lehmann, Christine Hanson, Kirsten K. Lin, Jing-wen Rousseau, Kimberly Carvalho, Filomena A. van der Linden, Wouter A. Santos, Nuno C. Bogyo, Matthew Khan, Shahid M. Heussler, Volker Sinnis, Photini |
| description |
:© 2017 Hopp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z 2018-05-25T14:50:55Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/33661 |
| url |
http://hdl.handle.net/10451/33661 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
PLOS Pathogens, 2017, September 18, 2017, e1006586 1553-7366 10.1371/journal.ppat.1006586 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Public Library of Science |
| publisher.none.fl_str_mv |
Public Library of Science |
| dc.source.none.fl_str_mv |
reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia instacron:RCAAP |
| instname_str |
FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia |
| instacron_str |
RCAAP |
| institution |
RCAAP |
| reponame_str |
Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| collection |
Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| repository.name.fl_str_mv |
Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia |
| repository.mail.fl_str_mv |
info@rcaap.pt |
| _version_ |
1833601545958064128 |