Host PI(3, 5)P2 Activity Is Required for Plasmodium berghei Growth During Liver Stage Infection. (21st August 2014)

• Record Type: Journal Article
• Authors: Thieleke‐Matos, Carolina; da Silva, Mafalda Lopes; Cabrita‐Santos, Laura; Pires, Cristiana F.; Ramalho, José S.; Ikonomov, Ognian; Seixas, Elsa; Shisheva, Assia; Seabra, Miguel C.; Barral, Duarte C.
• Is Part Of: Traffic. Volume 15:Number 10(2014:Oct.)
• Page Start: 1066
• Page End: 1082
• Publication Date: 2014-08-21
• Subjects: Biological transport -- Periodicals; 571.6
• DOI: 10.1111/tra.12190
• Languages: English
• ISSNs: 1398-9219

Abstract

<abstract abstract-type="main" id="tra12190-abs-0001"> <title>Abstract</title> <p id="tra12190-para-0001">Malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. In the host hepatocytes, the parasite is enclosed by a parasitophorous vacuole membrane (PVM). Here, we dissected the interaction between the <italic>Plasmodium</italic> parasite and the host cell late endocytic pathway and show that parasite growth is dependent on the phosphoinositide 5‐kinase (PIKfyve) that converts phosphatidylinositol 3‐phosphate [PI(3)P] into phosphatidylinositol 3, 5‐bisphosphate [PI(3, 5)P₂] in the endosomal system. We found that inhibition of PIKfyve by either pharmacological or non‐pharmacological means causes a delay in parasite growth. Moreover, we show that the PI(3, 5)P₂ effector protein TRPML1 that is involved in late endocytic membrane fusion, is present in vesicles closely contacting the PVM and is necessary for parasite growth. Thus, our studies suggest that the parasite PVM is able to fuse with host late endocytic vesicles in a PI(3, 5)P₂‐dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection.</p> <p> <inline-graphic xlink:href="ark:/27927/pgh1c9m0x2p" mimetype="image" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /> </p> </abstract>