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 (2020). A Plasmodium cysteine protease required for efficient transition from the liver infection stage. PLoS pathogens, 16(9), e1008891. Public Library of Science 10.1371/journal.ppat.1008891

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria
08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1553-7366

Publisher:

Public Library of Science

Funders:

[UNSPECIFIED] Deutsche Forschungsgemeinschaft HE 4497/1

Language:

English

Submitter:

Volker Heussler

Date Deposited:

15 Oct 2020 16:39

Last Modified:

15 Oct 2020 16:39

Publisher DOI:

10.1371/journal.ppat.1008891

PubMed ID:

32956401

BORIS DOI:

10.7892/boris.147063

URI:

https://boris.unibe.ch/id/eprint/147063

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