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

Research output: Contribution to journalArticle

108 Citations (Scopus)

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
StatePublished - May 8 2009

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Calpain
Toxoplasma
Parasites
Plasmodium falciparum
Genetic Suppression
Plasmodium
Toxoplasmosis
Vacuoles
Small Interfering RNA
Malaria
Peptide Hydrolases
Fibroblasts
Erythrocytes
Pharmacology
Morbidity
Mortality

ASJC Scopus subject areas

  • General

Cite this

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

Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells. / Chandramohanadas, Rajesh; Davis, Paul H.; Beiting, Daniel P.; Harbut, Michael B.; Darling, Claire; Velmourougane, Geetha; Lee, Ming Yeh; Greer, Peter A.; Roos, David S.; Greenbaum, Doron C.

In: Science, Vol. 324, No. 5928, 08.05.2009, p. 794-797.

Research output: Contribution to journalArticle

Chandramohanadas, R, Davis, PH, Beiting, DP, Harbut, MB, Darling, C, Velmourougane, G, Lee, MY, Greer, PA, Roos, DS & Greenbaum, DC 2009, 'Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells', Science, vol. 324, no. 5928, pp. 794-797. https://doi.org/10.1126/science.1171085
Chandramohanadas R, Davis PH, Beiting DP, Harbut MB, Darling C, Velmourougane G et al. Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells. Science. 2009 May 8;324(5928):794-797. https://doi.org/10.1126/science.1171085
Chandramohanadas, Rajesh ; Davis, Paul H. ; Beiting, Daniel P. ; Harbut, Michael B. ; Darling, Claire ; Velmourougane, Geetha ; Lee, Ming Yeh ; Greer, Peter A. ; Roos, David S. ; Greenbaum, Doron C. / Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells. In: Science. 2009 ; Vol. 324, No. 5928. pp. 794-797.
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