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Ectopic expression of a Neospora caninum Kazal type inhibitor triggers developmental defects in Toxoplasma and Plasmodium.
- Source :
-
PloS one [PLoS One] 2015 Mar 24; Vol. 10 (3), pp. e0121379. Date of Electronic Publication: 2015 Mar 24 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Regulated proteolysis is known to control a variety of vital processes in apicomplexan parasites including invasion and egress of host cells. Serine proteases have been proposed as targets for drug development based upon inhibitor studies that show parasite attenuation and transmission blockage. Genetic studies suggest that serine proteases, such as subtilisin and rhomboid proteases, are essential but functional studies have proved challenging as active proteases are difficult to express. Proteinaceous Protease Inhibitors (PPIs) provide an alternative way to address the role of serine proteases in apicomplexan biology. To validate such an approach, a Neospora caninum Kazal inhibitor (NcPI-S) was expressed ectopically in two apicomplexan species, Toxoplasma gondii tachyzoites and Plasmodium berghei ookinetes, with the aim to disrupt proteolytic processes taking place within the secretory pathway. NcPI-S negatively affected proliferation of Toxoplasma tachyzoites, while it had no effect on invasion and egress. Expression of the inhibitor in P. berghei zygotes blocked their development into mature and invasive ookinetes. Moreover, ultra-structural studies indicated that expression of NcPI-S interfered with normal formation of micronemes, which was also confirmed by the lack of expression of the micronemal protein SOAP in these parasites. Our results suggest that NcPI-S could be a useful tool to investigate the function of proteases in processes fundamental for parasite survival, contributing to the effort to identify targets for parasite attenuation and transmission blockage.
- Subjects :
- Cloning, Molecular
DNA Primers genetics
Drug Delivery Systems methods
Drug Discovery methods
Ectopic Gene Expression physiology
Fluorescent Antibody Technique, Indirect
Immunoblotting
Microscopy, Electron, Transmission
Plasmids genetics
Plasmodium berghei drug effects
Plasmodium berghei metabolism
Proteolysis
Serine Proteinase Inhibitors pharmacology
Toxoplasma drug effects
Toxoplasma metabolism
Transfection
Neospora metabolism
Plasmodium berghei growth & development
Serine Proteinase Inhibitors metabolism
Toxoplasma growth & development
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25803874
- Full Text :
- https://doi.org/10.1371/journal.pone.0121379