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Published on: February 8, 2012
Roles of proteases during invasion and egress by Plasmodium and Toxoplasma
Timothy J Dowse1, Konstantinos Koussis, Michael J Blackman
1Department of Biological Sciences, Imperial College, London, UK.
Abstract:
Apicomplexan pathogens replicate exclusively within the confines of a host cell. Entry into (invasion) and exit from (egress) these cells requires an array of specialized parasite molecules, many of which have long been considered to have potential as targets of drug or vaccine-based therapies. In this chapter the authors discuss the current state of knowledge regarding the role of parasite proteolytic enzymes in these critical steps in the life cycle of two clinically important apicomplexan genera, Plasmodium and Toxoplasma. At least three distinct proteases of the cysteine mechanistic class have been implicated in egress of the malaria parasite from cells of its vertebrate and insect host. In contrast, the bulk of the evidence indicates a prime role for serine proteases of the subtilisin and rhomboid families in invasion by both parasites. Whereas proteases involved in egress may function predominantly to degrade host cell structures, proteases involved in invasion probably act primarily as maturases and 'sheddases', required to activate and ultimately remove ligands involved in interactions with the host cell.
Insights
Proteolytic enzymes are crucial for apicomplexan parasite invasion and egress. Cysteine proteases aid malaria parasite egress, while serine proteases facilitate invasion by Plasmodium and Toxoplasma.
Area of Science:
- Parasitology
- Molecular Biology
- Biochemistry
Background:
- Apicomplexan pathogens like Plasmodium and Toxoplasma infect host cells.
- Parasite invasion and egress are essential for their life cycle.
- Proteolytic enzymes are potential drug and vaccine targets.
Purpose of the Study:
- To review the role of parasite proteolytic enzymes in apicomplexan invasion and egress.
- To focus on Plasmodium and Toxoplasma genera.
- To discuss cysteine and serine proteases.
Main Methods:
- Literature review of existing research on apicomplexan proteases.
- Analysis of the functions of different protease classes (cysteine, serine).
- Comparison of protease roles in invasion versus egress.
Main Results:
- Cysteine proteases are implicated in the egress of Plasmodium from host cells.
- Serine proteases (subtilisin and rhomboid families) are key for invasion by Plasmodium and Toxoplasma.
- Proteases involved in egress degrade host cell structures.
- Proteases involved in invasion act as maturases and shedases.
Conclusions:
- Proteolytic enzymes play distinct roles in apicomplexan invasion and egress.
- Targeting these proteases could lead to novel therapeutic strategies.
- Further research into apicomplexan proteases is warranted for drug and vaccine development.
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