Host PI(3,5)P 2 activity is required for Plasmodium berghei growth during liver stage infection

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13 Citations (Scopus)

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)P 2 ] 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)P 2 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)P 2 -dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection.

Original languageEnglish
Pages (from-to)1066-1082
Number of pages17
JournalTraffic
Volume15
Issue number10
DOIs
Publication statusPublished - 1 Oct 2014

Fingerprint

Plasmodium berghei
Liver
Parasites
Growth
Infection
Vacuoles
Membranes
Transport Vesicles
Membrane Fusion
1-Phosphatidylinositol 4-Kinase
Plasmodium
Electric fuses
Phosphatidylinositols
Malaria
Hepatocytes
Phosphotransferases
Fusion reactions
Erythrocytes
Pharmacology

Keywords

  • Liver stage infection
  • Malaria
  • PI(3,5)P
  • PIKfyve
  • Plasmodium berghei
  • TRPML1

Cite this

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title = "Host PI(3,5)P 2 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)P 2 ] 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)P 2 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)P 2 -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)P, PIKfyve, Plasmodium berghei, TRPML1",
author = "Carolina Thieleke-Matos and {da Silva}, {Mafalda Lopes} and Laura Cabrita-Santos and Pires, {Cristiana F.} and Ramalho, {Jos{\'e} S.} and Ognian Ikonomov and Elsa Seixas and Assia Shisheva and Seabra, {Miguel C.} and Barral, {Duarte C.}",
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TY - JOUR

T1 - Host PI(3,5)P 2 activity is required for Plasmodium berghei growth during liver stage infection

AU - Thieleke-Matos, Carolina

AU - da Silva, Mafalda Lopes

AU - Cabrita-Santos, Laura

AU - Pires, Cristiana F.

AU - Ramalho, José S.

AU - Ikonomov, Ognian

AU - Seixas, Elsa

AU - Shisheva, Assia

AU - Seabra, Miguel C.

AU - Barral, Duarte C.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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)P 2 ] 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)P 2 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)P 2 -dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection.

AB - 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)P 2 ] 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)P 2 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)P 2 -dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection.

KW - Liver stage infection

KW - Malaria

KW - PI(3,5)P

KW - PIKfyve

KW - Plasmodium berghei

KW - TRPML1

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