Exit of Plasmodium Sporozoites from Oocysts Is an Active Process That Involves the Circumsporozoite Protein
Open Access
- 30 September 2005
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Pathogens
- Vol. 1 (1), e9
- https://doi.org/10.1371/journal.ppat.0010009
Abstract
Plasmodium sporozoites develop within oocysts residing in the mosquito midgut. Mature sporozoites exit the oocysts, enter the hemolymph, and invade the salivary glands. The circumsporozoite (CS) protein is the major surface protein of salivary gland and oocyst sporozoites. It is also found on the oocyst plasma membrane and on the inner surface of the oocyst capsule. CS protein contains a conserved motif of positively charged amino acids: region II-plus, which has been implicated in the initial stages of sporozoite invasion of hepatocytes. We investigated the function of region II-plus by generating mutant parasites in which the region had been substituted with alanines. Mutant parasites produced normal numbers of sporozoites in the oocysts, but the sporozoites were unable to exit the oocysts. In in vitro as well, there was a profound delay, upon trypsin treatment, in the release of mutant sporozoites from oocysts. We conclude that the exit of sporozoites from oocysts is an active process that involves the region II-plus of CS protein. In addition, the mutant sporozoites were not infective to young rats. These findings provide a new target for developing reagents that interfere with the transmission of malaria. Malaria affects hundreds of millions of people, and kills at least 1 million children per year. The infective stages of the malaria parasites, named “sporozoites,” are found in the salivary gland of Anopheles mosquitoes, and are injected along with the saliva during blood feeding. From the skin, sporozoites enter the blood circulation and invade liver cells where the parasites multiply. When they exit the liver, these parasites infect blood cells and can cause severe symptoms. If ingested by mosquitoes, the blood-stage parasites continue their lifecycle in the insect stomach. Thousands of sporozoites are formed within a cyst-like structure (oocyst). The sporozoites come out of the oocyst and infect the salivary gland, where they remain until injected back into humans. Malaria parasites are increasingly resistant to drugs, mosquitoes are difficult to eliminate, and effective vaccines are not yet available. New tools to combat malaria are urgently needed. One exciting approach, although the application is in the distant future, is to release in endemic areas genetically modified mosquitoes that are resistant to parasite growth. This paper provides a new target for generating these “transmission-block” mosquitoes and shows that the exit of sporozoites from the oocysts is an active process that requires the enzymatic digestion of components of the oocyst wall. If these enzymes are inhibited in transgenic mosquitoes, sporozoites will never reach the salivary gland.Keywords
This publication has 34 references indexed in Scilit:
- A malarial cysteine protease is necessary for Plasmodium sporozoite egress from oocystsThe Journal of Experimental Medicine, 2005
- PLASMODIUMSPOROZOITE MOLECULAR CELL BIOLOGYAnnual Review of Cell and Developmental Biology, 2004
- A Multidomain Adhesion Protein Family Expressed inPlasmodium falciparumIs Essential for Transmission to the MosquitoThe Journal of Experimental Medicine, 2004
- Molecular interactions betweenPlasmodiumand its insect vectorsCellular Microbiology, 2002
- The Binding of the Circumsporozoite Protein to Cell Surface Heparan Sulfate Proteoglycans Is Required for PlasmodiumSporozoite Attachment to Target CellsJournal of Biological Chemistry, 2001
- Circumsporozoite protein is required for development of malaria sporozoites in mosquitoesNature, 1997
- Biosynthesis of Pb44, the protective antigen of sporozoites of Plasmodium berghei.The Journal of Experimental Medicine, 1981
- Excystment by sporozoites of malaria parasitesNature, 1974
- Studies on the Motility of Plasmodium Sporozoites*The Journal of Protozoology, 1974
- DIFFERENTIATION OF NUCLEAR AND CYTOPLASMIC FINE STRUCTURE DURING SPOROGONIC DEVELOPMENT OF PLASMODIUM BERGHEI The Journal of cell biology, 1967