Science. 2009 Apr 2. [Epub ahead of print]
Apicomplexan Parasites Co-Opt Host Calpains to Facilitate Their Escape from Infected Cells
Chandramohanadas R, Davis PH, Beiting DP, Harbut MB, Darling C, Velmourougane G, Lee MY, Greer PA, Roos DS, Greenbaum DC.
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Apicomplexan parasites, including Plasmodium falciparum and Toxoplasma gondii (the causative agents of malaria and toxoplasmosis, respectively) are responsible for significant morbidity and mortality worldwide. These pathogenic protozoa replicate within an intracellular vacuole inside infected host cells, from which they must escape to initiate a new lytic cycle. Integrating cell biological, pharmacological and genetic approaches, we provide evidence that both Plasmodium and Toxoplasma hijack host cell calpain proteases to facilitate parasite egress. Immunodepletion or inhibition of calpain-1 in hypotonically lysed and resealed erythrocytes prevented the escape of P. falciparum parasites, which was restored by adding purified calpain-1. Similarly, efficient egress of T. gondii from mammalian fibroblasts was blocked by either siRNA-mediated suppression or genetic deletion of calpain activity, and could be restored by genetic complementation.
PMID: 19342550 [PubMed - as supplied by publisher]