Report

Apicomplexan Parasites Co-Opt Host Calpains to Facilitate Their Escape from Infected Cells

Science  08 May 2009:
Vol. 324, Issue 5928, pp. 794-797
DOI: 10.1126/science.1171085

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


This article has a correction. Please see:

Let Me Out

Apicomplexan parasites like Plasmodium falciparum, which causes malaria, and Toxoplasma gondii, which cause toxoplasmosis, replicate inside animal host cells. In order for infections to spread successfully within the host from cell to cell, daughter parasites after replication need to be able to escape from their incubator cell. In the course of studies intended to elucidate the functions of proteases during parasite infection, Chandramohanadas et al. (p. 794, published online 2 April) noted that host cell calpain is the only protease present at the right time and place to facilitate the egress of malaria parasites from infected red blood cells. Parasite egress from infected resealed erythrocytes was prevented when calpain was removed. Moreover, T. gondii was unable to escape efficiently from murine fibroblast knockouts lacking a calpain regulatory subunit.

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.

View Full Text

Cited By...