Coordinated protease activity is essential to parasite survival. Throughout its life cycle, the Plasmodium parasite expresses a potent cysteine protease inhibitor that has the potential to inhibit parasite as well as host cell cysteine proteases. We have generated a stage-specific knockout of this inhibitor and were able to analyze its function in all life cycle stages. Interestingly, although constitutively expressed, the inhibitor primarily appears to play an important role in sporozoite gliding, liver stage development and egress from hepatocytes whereas blood stage parasites lacking the inhibitor exhibited only mild attenuation. Parasite sexual stage development was not affected and development continued normally within the mosquito. However, sporozoites lacking the inhibitor show a strong phenotype; they are completely blocked in motility and thus cannot transmigrate or invade cells. Complementation of knockout parasites by exogenous expression of the inhibitor completely restored parasite virulence.
Vyšlo v časopise: A Cysteine Protease Inhibitor of Is Essential for Exo-erythrocytic Development. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004336 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004336
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