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Infection and Immunity, May 2005, p. 2704-2708, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2704-2708.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Acanthamoeba castellanii Induces Host Cell Death via a Phosphatidylinositol 3-Kinase-Dependent Mechanism

James Sissons,1 Kwang Sik Kim,2 Monique Stins,2 Samantha Jayasekera,1 Selwa Alsam,1 and Naveed Ahmed Khan1*

School of Biological and Chemical Sciences, Birkbeck College, University of London, London, England, United Kingdom,1 Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland2

Received 18 June 2004/ Returned for modification 12 August 2004/ Accepted 7 January 2005

Granulomatous amoebic encephalitis due to Acanthamoeba castellanii is a serious human infection with fatal consequences, but it is not clear how the circulating amoebae interact with the blood-brain barrier and transmigrate into the central nervous system. We studied the effects of an Acanthamoeba encephalitis isolate belonging to the T1 genotype on human brain microvascular endothelial cells, which constitute the blood-brain barrier. Using an apoptosis-specific enzyme-linked immunosorbent assay, we showed that Acanthamoeba induces programmed cell death in brain microvascular endothelial cells. Next, we observed that Acanthamoeba specifically activates phosphatidylinositol 3-kinase. Acanthamoeba-mediated brain endothelial cell death was abolished using LY294002, a phosphatidylinositol 3-kinase inhibitor. These results were further confirmed using brain microvascular endothelial cells expressing dominant negative forms of phosphatidylinositol 3-kinase. This is the first demonstration that Acanthamoeba-mediated brain microvascular endothelial cell death is dependent on phosphatidylinositol 3-kinase.

* Corresponding author. Mailing address: School of Biological and Chemical Sciences, Birkbeck, College, University of London, London WC1E 7HX, England, United Kingdom. Phone: 44-(0)207-079-0797. Fax: 44-(0)207-631-6246. E-mail: n.khan{at}sbc.bbk.ac.uk.

Editor: J. F. Urban, Jr.

Infection and Immunity, May 2005, p. 2704-2708, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2704-2708.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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