MRC National Institute for Medical Research, London
Science for Health
Unique enzyme controls malaria parasite development - shape, movement and invasion
21 September 2012
Parasite transmission from one individual to another occurs when a mosquito takes a blood meal containing malarial gametocytes, which then transform into female and male gametes. Following fertilisation the zygote forms a motile ookinete. The ookinete burrows through the mosquito gut wall, and comes to rest on the other side where it develops into an oocyst to produce thousands of sporozoites that migrate to the mosquito's salivary glands ready for transmission to the next individual.
The phosphatase belongs to a family of proteins found only in bacteria, plants and algae and the alveolates, a large group of single-celled protozoa of which the malaria parasite is a member. The enzyme removes phosphate groups from proteins to control their function and is found largely in female gametocytes and ookinetes. Deletion of the gene encoding the phosphatase results in grossly abnormal ookinete development and loss of motility so that the parasite cannot cross the mosquito gut.
This work, funded by both the MRC and the Wellcome Trust, is part of a project lead by Rita Tewari at the Centre for Genetics and Genomics, Nottingham and Tony Holder (pictured) in NIMR's Division of Parasitology. The research is primarily funded by the MRC to establish the role of phosphatases in malarial parasite development.
Transmission through the mosquito represents a bottleneck in the parasite's life cycle. Therapeutic strategies to target these stages, will be essential to the long term goal to eradicate and finally eliminate malaria.
Tony Holder
This is the first step in understanding the functional role of phosphatases in malaria biology. Although considered promiscuous in their function they can be explored as good targets for malaria control and transmission blocking. The control of parasite transmission is important in order to prevent the spread of malaria and targeting PPKL can be an important player in this process.
Rita Tewari
The ookinete is no longer motile and its morphology is grossly disrupted as shown in this comparison of normal and phosphatase deficient parasites visualised by fluorescence light microscopy.
Original article
David S. Guttery, Benoit Poulin, David J. P. Ferguson, Balázs Szöőr, Bill Wickstead, Paula L. Carroll, Chandra Ramakrishnan, Declan Brady, Eva-Maria Patzewitz, Ursula Straschil, Lev Solyakov, Judith L. Green, Robert E. Sinden, Andrew B. Tobin, Anthony A. Holder, Rita Tewari (2012)
A unique protein phosphatase with kelch-like domains (PPKL) in Plasmodium modulates ookinete differentiation, motility and invasion
PLOS Pathogens 8(9): e1002948. Publisher fulltext.
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