Host PI(3,5)P2 Activity Is Required for Plasmodium berghei Growth During Liver Stage Infection |
| |
Authors: | Carolina Thieleke‐Matos Mafalda Lopes da Silva Laura Cabrita‐Santos Cristiana F. Pires José S. Ramalho Ognian Ikonomov Elsa Seixas Assia Shisheva Miguel C. Seabra Duarte C. Barral |
| |
Affiliation: | 1. CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, , 1169‐056 Lisboa, Portugal;2. IGC, Instituto Gulbenkian de Ciência, , 2780‐156 Oeiras, Portugal;3. Department of Physiology, Wayne State University School of Medicine, , Detroit, MI, 48201 USA;4. Molecular Medicine Section, National Heart and Lung Institute, Imperial College London, , London, SW7 2AZ UK |
| |
Abstract: | 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 Plasmodium 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. |
| |
Keywords: | liver stage infection malaria PI(3,5)P2 PIKfyve Plasmodium berghei TRPML1 |
|
|