Publication Date:
2009-04-04
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3391539/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3391539/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- F32 AI075846/AI/NIAID NIH HHS/ -- F32 AI075846-02/AI/NIAID NIH HHS/ -- F32 AI077268/AI/NIAID NIH HHS/ -- F32 AI077268-02/AI/NIAID NIH HHS/ -- R37 AI028724/AI/NIAID NIH HHS/ -- R37 AI028724-17/AI/NIAID NIH HHS/ -- T32 GM008076/GM/NIGMS NIH HHS/ -- T32 GM008076-24/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 May 8;324(5928):794-7. doi: 10.1126/science.1171085. Epub 2009 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342550" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calpain/blood/genetics/*metabolism
;
Cell Line
;
Cell Line, Tumor
;
Erythrocytes/*parasitology
;
Fibroblasts/parasitology
;
Humans
;
Leucine/analogs & derivatives/pharmacology
;
Life Cycle Stages
;
Merozoites/physiology
;
Mice
;
Mice, Knockout
;
Plasmodium falciparum/growth & development/metabolism/*pathogenicity/physiology
;
RNA, Small Interfering
;
Schizonts/physiology
;
Toxoplasma/growth & development/metabolism/*pathogenicity/physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
