scholarly journals A malaria parasite phospholipid flippase safeguards midgut traversal of ookinetes for mosquito transmission

2021 ◽  
Vol 7 (30) ◽  
pp. eabf6015
Author(s):  
Zhenke Yang ◽  
Yang Shi ◽  
Huiting Cui ◽  
Shuzhen Yang ◽  
Han Gao ◽  
...  

Mosquito midgut epithelium traversal is essential for malaria parasite transmission. Phospholipid flippases are eukaryotic type 4 P-type adenosine triphosphatases (P4-ATPases), which, in association with CDC50, translocate phospholipids across the membrane lipid bilayers. In this study, we investigated the function of a putative P4-ATPase, ATP7, from the rodent malaria parasite Plasmodium yoelii. Disruption of ATP7 blocks the parasite infection of mosquitoes. ATP7 is localized on the ookinete plasma membrane. While ATP7-depleted ookinetes are capable of invading the midgut, they are eliminated within the epithelial cells by a process independent from the mosquito complement-like immunity. ATP7 colocalizes and interacts with the flippase cofactor CDC50C. Depletion of CDC50C phenocopies ATP7 deficiency. ATP7-depleted ookinetes fail to uptake phosphatidylcholine across the plasma membrane. Ookinete microinjection into the mosquito hemocoel reverses the ATP7 deficiency phenotype. Our study identifies Plasmodium flippase as a mechanism of parasite survival in the midgut epithelium that is required for mosquito transmission.

2021 ◽  
Author(s):  
Zhenke Yang ◽  
Yang Shi ◽  
Huiting Cui ◽  
Shuzhen Yang ◽  
Han Gao ◽  
...  

Mosquito midgut epithelium traversal is an essential component of transmission of malaria parasites. Phospholipid flippases are eukaryotic type IV ATPases (P4-ATPases), which in association with CDC50 cofactors, translocate phospholipids across lipid bilayers to maintain the membrane asymmetry. In this study, we investigated the function of a putative P4-ATPase, ATP7, from the rodent malaria parasite P. yoelii. Disruption of ATP7 results in block of parasite infection of mosquitoes. ATP7 is localized on the ookinete plasma membrane. While ATP7-depleted ookinetes are motile and capable of invading the midgut, they are quickly eliminated within the epithelial cells by a process that is independent from the mosquito complement-like immunity. ATP7 colocalizes and interacts with the flippase co-factor CDC50C. Importantly, depletion of CDC50C phenocopies ATP7 deficiency. ATP7-depleted ookinetes fail to translocate phosphatidylcholine (PC) across the plasma membrane, resulting in PC exposure at the ookinete surface. Lastly, ookinete microinjection into the mosquito hemocoel reverses the ATP7 deficiency phenotype. Our study identifies Plasmodium flippase as a novel mechanism of parasite survival in the midgut epithelium that is required for mosquito transmission.


2003 ◽  
Vol 33 (13) ◽  
pp. 1455-1461 ◽  
Author(s):  
Shin-ichiro Kawazu ◽  
Tomoyoshi Nozaki ◽  
Takafumi Tsuboi ◽  
Yoko Nakano ◽  
Kanako Komaki-Yasuda ◽  
...  

2006 ◽  
Vol 146 (2) ◽  
pp. 242-250 ◽  
Author(s):  
Artemio M. Jongco ◽  
Li-Min Ting ◽  
Vandana Thathy ◽  
Maria M. Mota ◽  
Kami Kim

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e50780 ◽  
Author(s):  
Kazuhide Yahata ◽  
Moritz Treeck ◽  
Richard Culleton ◽  
Tim-Wolf Gilberger ◽  
Osamu Kaneko

Parasitology ◽  
1984 ◽  
Vol 89 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Lindsey J. Panton ◽  
G. Knowles ◽  
D. Walliker

SummaryAntigens of three lines of the rodent malaria parasitePlasmodium yoeliihave been studied using crossed immunoelectrophoresis.P. y. yoeliiline A1is a mild line which is restricted to reticulocytes.P. y. yoeliiline YM andP. y. nigeriensisline D1are virulent infections which multiply in both immature and mature erythrocytes. One antigen, designated Py-1, was found to differ in its electrophoretic mobility between the lines, being fast (F) in lines A1and YM and slow (S) in line D1. Antigen Py-1 also varied in quantity among the three lines; greater amounts were detected in parasites inhabiting mature erythrocytes than in those in reticulocytes. These characters were stable during blood and mosquito passage.


Nature ◽  
2002 ◽  
Vol 419 (6906) ◽  
pp. 512-519 ◽  
Author(s):  
Jane M. Carlton ◽  
Samuel V. Angiuoli ◽  
Bernard B. Suh ◽  
Taco W. Kooij ◽  
Mihaela Pertea ◽  
...  

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