Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells

Rajesh Chandramohanadas, Paul H. Davis, Daniel P. Beiting, Michael B. Harbut, Claire Darling, Geetha Velmourougane, Ming Yeh Lee, Peter A. Greer, David S. Roos, Doron C. Greenbaum

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108 Scopus citations

Abstract

Apicomplexan parasites, including Plasmodium falciparum and Toxoplasma gondii (the causative agents of malaria and toxoplasmosis, respectively), are responsible for considerable morbidity and mortality worldwide. These pathogenic protozoa replicate within an intracellular vacuole inside of infected host cells, from which they must escape to initiate a new lytic cycle. By 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 small interfering RNA-mediated suppression or genetic deletion of calpain activity and could be restored by genetic complementation.

Original languageEnglish (US)
Pages (from-to)794-797
Number of pages4
JournalScience
Volume324
Issue number5928
DOIs
Publication statusPublished - May 8 2009

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Chandramohanadas, R., Davis, P. H., Beiting, D. P., Harbut, M. B., Darling, C., Velmourougane, G., ... Greenbaum, D. C. (2009). Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells. Science, 324(5928), 794-797. https://doi.org/10.1126/science.1171085