A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development

Lehmann, Christine; Heitmann, Anna; Mishra, Satish; Burda, Paul-Christian; Singer, Mirko; Prado, Monica; Niklaus, Livia; Lacroix, Céline; Ménard, Robert; Frischknecht, Friedrich; Stanway, Rebecca; Sinnis, Photini; Heussler, Volker (2014). A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development. PLoS pathogens, 10(8), e1004336. Public Library of Science 10.1371/journal.ppat.1004336

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Plasmodium parasites express a potent inhibitor of cysteine proteases (ICP) throughout their life cycle. To analyze the role of ICP in different life cycle stages, we generated a stage-specific knockout of the Plasmodium berghei ICP (PbICP). Excision of the pbicb gene occurred in infective sporozoites and resulted in impaired sporozoite invasion of hepatocytes, despite residual PbICP protein being detectable in sporozoites. The vast majority of these parasites invading a cultured hepatocyte cell line did not develop to mature liver stages, but the few that successfully developed hepatic merozoites were able to initiate a blood stage infection in mice. These blood stage parasites, now completely lacking PbICP, exhibited an attenuated phenotype but were able to infect mosquitoes and develop to the oocyst stage. However, PbICP-negative sporozoites liberated from oocysts exhibited defective motility and invaded mosquito salivary glands in low numbers. They were also unable to invade hepatocytes, confirming that control of cysteine protease activity is of critical importance for sporozoites. Importantly, transfection of PbICP-knockout parasites with a pbicp-gfp construct fully reversed these defects. Taken together, in P. berghei this inhibitor of the ICP family is essential for sporozoite motility but also appears to play a role during parasite development in hepatocytes and erythrocytes.

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

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Burda, Paul-Christian; Niklaus, Livia; Limenitakis Stanway, Rebecca and Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1553-7366

Publisher:

Public Library of Science

Language:

English

Submitter:

Volker Heussler

Date Deposited:

14 Aug 2015 11:55

Last Modified:

02 Sep 2015 11:35

Publisher DOI:

10.1371/journal.ppat.1004336

PubMed ID:

25166051

BORIS DOI:

10.7892/boris.71013

URI:

https://boris.unibe.ch/id/eprint/71013

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