Inhibitor of Cysteine Proteases Is Critical for Motility and Infectivity of <italic toggle="yes">Plasmodium</italic> Sporozoites

ABSTRACT Malaria is transmitted when motile sporozoites are injected into the dermis by an infected female Anopheles mosquito. Inside the mosquito vector, sporozoites egress from midgut-associated oocysts and eventually penetrate the acinar cells of salivary glands. Parasite-encoded factors with exc...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Katja E. Boysen, Kai Matuschewski
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7c34376404e0403d933b29cfa39105ab
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7c34376404e0403d933b29cfa39105ab
record_format	dspace
spelling	oai:doaj.org-article:7c34376404e0403d933b29cfa39105ab2021-11-15T15:42:31ZInhibitor of Cysteine Proteases Is Critical for Motility and Infectivity of <italic toggle="yes">Plasmodium</italic> Sporozoites10.1128/mBio.00874-132150-7511https://doaj.org/article/7c34376404e0403d933b29cfa39105ab2013-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00874-13https://doaj.org/toc/2150-7511ABSTRACT Malaria is transmitted when motile sporozoites are injected into the dermis by an infected female Anopheles mosquito. Inside the mosquito vector, sporozoites egress from midgut-associated oocysts and eventually penetrate the acinar cells of salivary glands. Parasite-encoded factors with exclusive vital roles in the insect vector can be studied by classical reverse genetics. Here, we characterized the in vivo roles of Plasmodium berghei falstatin/ICP (inhibitor of cysteine proteases). This protein was previously suggested to act as a protease inhibitor during erythrocyte invasion. We show by targeted gene disruption that loss of ICP function does not affect growth inside the mammalian host but causes a complete defect in sporozoite transmission. Sporogony occurred normally in icp(−) parasites, but hemocoel sporozoites showed a defect in continuous gliding motility and infectivity for salivary glands, which are prerequisites for sporozoite transmission to the mammalian host. Absence of ICP correlates with enhanced cleavage of circumsporozoite protein, in agreement with a role as a protease regulator. We conclude that ICP is essential for only the final stages of sporozoite maturation inside the mosquito vector. This study is the first genetic evidence that an ICP is necessary for the productive motility of a eukaryotic parasitic cell. IMPORTANCE Cysteine proteases and their inhibitors are considered ideal drug targets for the treatment of a wide range of diseases, including cancer and parasitic infections. In protozoan parasites, including Leishmania, Trypanosoma, and Plasmodium, cysteine proteases play important roles in life cycle progression. A mouse malaria model provides an unprecedented opportunity to study the roles of a parasite-encoded inhibitor of cysteine proteases (ICP) over the entire parasite life cycle. By precise gene deletion, we found no evidence that ICP influences disease progression or parasite virulence. Instead, we discovered that this factor is necessary for parasite movement and malaria transmission from mosquitoes to mammals. This finding in a fast-moving unicellular protozoan has important implications for malaria intervention strategies and the roles of ICPs in the regulation of eukaryotic cell migration.Katja E. BoysenKai MatuschewskiAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 6 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Katja E. Boysen Kai Matuschewski Inhibitor of Cysteine Proteases Is Critical for Motility and Infectivity of <italic toggle="yes">Plasmodium</italic> Sporozoites
description	ABSTRACT Malaria is transmitted when motile sporozoites are injected into the dermis by an infected female Anopheles mosquito. Inside the mosquito vector, sporozoites egress from midgut-associated oocysts and eventually penetrate the acinar cells of salivary glands. Parasite-encoded factors with exclusive vital roles in the insect vector can be studied by classical reverse genetics. Here, we characterized the in vivo roles of Plasmodium berghei falstatin/ICP (inhibitor of cysteine proteases). This protein was previously suggested to act as a protease inhibitor during erythrocyte invasion. We show by targeted gene disruption that loss of ICP function does not affect growth inside the mammalian host but causes a complete defect in sporozoite transmission. Sporogony occurred normally in icp(−) parasites, but hemocoel sporozoites showed a defect in continuous gliding motility and infectivity for salivary glands, which are prerequisites for sporozoite transmission to the mammalian host. Absence of ICP correlates with enhanced cleavage of circumsporozoite protein, in agreement with a role as a protease regulator. We conclude that ICP is essential for only the final stages of sporozoite maturation inside the mosquito vector. This study is the first genetic evidence that an ICP is necessary for the productive motility of a eukaryotic parasitic cell. IMPORTANCE Cysteine proteases and their inhibitors are considered ideal drug targets for the treatment of a wide range of diseases, including cancer and parasitic infections. In protozoan parasites, including Leishmania, Trypanosoma, and Plasmodium, cysteine proteases play important roles in life cycle progression. A mouse malaria model provides an unprecedented opportunity to study the roles of a parasite-encoded inhibitor of cysteine proteases (ICP) over the entire parasite life cycle. By precise gene deletion, we found no evidence that ICP influences disease progression or parasite virulence. Instead, we discovered that this factor is necessary for parasite movement and malaria transmission from mosquitoes to mammals. This finding in a fast-moving unicellular protozoan has important implications for malaria intervention strategies and the roles of ICPs in the regulation of eukaryotic cell migration.
format	article
author	Katja E. Boysen Kai Matuschewski
author_facet	Katja E. Boysen Kai Matuschewski
author_sort	Katja E. Boysen
title	Inhibitor of Cysteine Proteases Is Critical for Motility and Infectivity of <italic toggle="yes">Plasmodium</italic> Sporozoites
title_short	Inhibitor of Cysteine Proteases Is Critical for Motility and Infectivity of <italic toggle="yes">Plasmodium</italic> Sporozoites
title_full	Inhibitor of Cysteine Proteases Is Critical for Motility and Infectivity of <italic toggle="yes">Plasmodium</italic> Sporozoites
title_fullStr	Inhibitor of Cysteine Proteases Is Critical for Motility and Infectivity of <italic toggle="yes">Plasmodium</italic> Sporozoites
title_full_unstemmed	Inhibitor of Cysteine Proteases Is Critical for Motility and Infectivity of <italic toggle="yes">Plasmodium</italic> Sporozoites
title_sort	inhibitor of cysteine proteases is critical for motility and infectivity of <italic toggle="yes">plasmodium</italic> sporozoites
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/7c34376404e0403d933b29cfa39105ab
work_keys_str_mv	AT katjaeboysen inhibitorofcysteineproteasesiscriticalformotilityandinfectivityofitalictoggleyesplasmodiumitalicsporozoites AT kaimatuschewski inhibitorofcysteineproteasesiscriticalformotilityandinfectivityofitalictoggleyesplasmodiumitalicsporozoites
_version_	1718427593931227136

Inhibitor of Cysteine Proteases Is Critical for Motility and Infectivity of <italic toggle="yes">Plasmodium</italic> Sporozoites

Ejemplares similares