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

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 sporozoit...

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Autores principales:	Christine Lehmann, Anna Heitmann, Satish Mishra, Paul-Christian Burda, Mirko Singer, Monica Prado, Livia Niklaus, Céline Lacroix, Robert Ménard, Friedrich Frischknecht, Rebecca Stanway, Photini Sinnis, Volker Heussler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6aef6bf9991644ef8a83e2ca92eb41e0
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spelling	oai:doaj.org-article:6aef6bf9991644ef8a83e2ca92eb41e02021-11-25T05:46:07ZA cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.1553-73661553-737410.1371/journal.ppat.1004336https://doaj.org/article/6aef6bf9991644ef8a83e2ca92eb41e02014-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25166051/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Plasmodium 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.Christine LehmannAnna HeitmannSatish MishraPaul-Christian BurdaMirko SingerMonica PradoLivia NiklausCéline LacroixRobert MénardFriedrich FrischknechtRebecca StanwayPhotini SinnisVolker HeusslerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 8, p e1004336 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Christine Lehmann Anna Heitmann Satish Mishra Paul-Christian Burda Mirko Singer Monica Prado Livia Niklaus Céline Lacroix Robert Ménard Friedrich Frischknecht Rebecca Stanway Photini Sinnis Volker Heussler A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.
description	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.
format	article
author	Christine Lehmann Anna Heitmann Satish Mishra Paul-Christian Burda Mirko Singer Monica Prado Livia Niklaus Céline Lacroix Robert Ménard Friedrich Frischknecht Rebecca Stanway Photini Sinnis Volker Heussler
author_facet	Christine Lehmann Anna Heitmann Satish Mishra Paul-Christian Burda Mirko Singer Monica Prado Livia Niklaus Céline Lacroix Robert Ménard Friedrich Frischknecht Rebecca Stanway Photini Sinnis Volker Heussler
author_sort	Christine Lehmann
title	A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.
title_short	A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.
title_full	A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.
title_fullStr	A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.
title_full_unstemmed	A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.
title_sort	cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6aef6bf9991644ef8a83e2ca92eb41e0
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A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.

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