Host PI(3,5)P2 activity is required for Plasmodium berghei growth during liver stage infection.

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.

• 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
• Journal: Traffic (Copenhagen, Denmark) (Traffic) Vol. 15 Issue 10 Pg. 1066-82 (Oct 2014) ISSN: 1600-0854 [Electronic] England
• PMID: 24992508 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Mcoln1 protein, mouse
• Phosphatidylinositol Phosphates
• Phosphoinositide-3 Kinase Inhibitors
• Transient Receptor Potential Channels
• phosphatidylinositol 3,5-diphosphate
• Pikfyve protein, mouse

Topics

• Animals
• Cell Line, Tumor
• Endocytosis
• Liver (metabolism, parasitology)
• Mice
• Parasite Load
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphatidylinositol Phosphates (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Plasmodium berghei (pathogenicity, physiology)
• Protein Transport
• Transient Receptor Potential Channels (metabolism)