Open AccessPerforin‐like protein PPLP 2 permeabilizes the red blood cell membrane during egress of P lasmodium falciparum gametocytes
Author(s) -
Wirth Christine C.,
Glushakova Svetlana,
Scheuermayer Matthias,
Repnik Urska,
Garg Swati,
Schaack Dominik,
Kachman Marika M.,
Weißbach Tim,
Zimmerberg Joshua,
Dandekar Thomas,
Griffiths Gareth,
Chitnis Chetan E.,
Singh Shailja,
Fischer Rainer,
Pradel Gabriele
Publication year - 2014
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12288
Subject(s) - gametocyte , biology , microbiology and biotechnology , cytoplasm , plasmodium falciparum , immunology , malaria
Summary Egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. Hence, we investigated the role of the plasmodial perforin‐like protein PPLP 2 in the egress of P lasmodium falciparum from erythrocytes. PPLP 2 is expressed in blood stage schizonts and mature gametocytes. The protein localizes in vesicular structures, which in activated gametocytes discharge PPLP 2 in a calcium‐dependent manner. PPLP 2 comprises a MACPF domain and recombinant PPLP 2 has haemolytic activities towards erythrocytes. PPLP 2‐deficient [ PPLP 2(−)] merozoites show normal egress dynamics during the erythrocytic replication cycle, but activated PPLP 2(−) gametocytes were unable to leave erythrocytes and stayed trapped within these cells. While the parasitophorous vacuole membrane ruptured normally, the activated PPLP 2(−) gametocytes were unable to permeabilize the erythrocyte membrane and to release the erythrocyte cytoplasm. In consequence, transmission of PPLP 2(−) parasites to the Anopheles vector was reduced. Pore‐forming equinatoxin II rescued both PPLP 2(−) gametocyte exflagellation and parasite transmission. The pore sealant Tetronic 90R4, on the other hand, caused trapping of activated wild‐type gametocytes within the enveloping erythrocytes, thus mimicking the PPLP 2(−) loss‐of‐function phenotype. We propose that the haemolytic activity of PPLP 2 is essential for gametocyte egress due to permeabilization of the erythrocyte membrane and depletion of the erythrocyte cytoplasm.