A Step Towards Defeating Malaria

Blogging on Peer-Reviewed ResearchA lectin is a funny little protein that seems to be used in a lot of biological systems. They bind to sugars, and one of the roles they play is inhibition of “agglutination” … clumping, or gluing together … of other molecules.

A sea cucumber is an echinoderm that lives in the ocean. It looks kind of like a cucumber, but if you saw a cucumber that looked and acted like an echinoderm you would probably not put it in your salad.

Malaria is a type of protozoan, a single celled organism that is not a bacteria. There are many kinds, and they complex life cycle with many different stages, including one stage that lives in the gut of a mosquito, and another stage that lives in the blood cells of a vertebrate host. One of the nasty forms of malaria that affects humans is Plasmodium falciparum.

An ookinete is the general name for a protozoan zygote. It is an egg that moves, as you can guess from its name. The malaria parasite is an ookinete when it enters the gut of a mosquito.

A sporozoite is the life stage of malaria when it has moved from the gut to the salivary glands, from where it is potentially passed to the vertebrate host when the mosquito is busy sucking blood.

A team of scientists, as reported in a paper by Yoshida et al, have created a transgenic mosquito (Anopheles stephensi) by inserting a gene that expresses the C-type lectin CEL-III, which is a lectin normally found in the sea cucumber Cucumaria echinata.

CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation … In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered [mosquitos] that affect the Plasmodium transmission … human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of … mosquitoes [that will effectively transmit] Plasmodium

This paper is published in PLoS Pathogens, and PLoS tends to provide very readable summaries:

Malaria is arguably the most important vector-borne disease worldwide, affecting 300 million people and killing 1-2 million people every year. The lack of an effective vaccine and the emergence of the parasites’ resistance to many existing anti-malarial drugs have aggravated the situation. Clearly, development of novel strategies for control of the disease is urgently needed. Mosquitoes are obligatory vectors for the disease and inhibition of parasite development in the mosquito has considerable promise as a new approach in the fight against malaria. Based on recent advances in the genetic engineering of mosquitoes, the concept of generating genetically modified (GM) mosquitoes that hinder transmission by either killing or interfering with parasite development is a potential means of controlling the disease. To generate these GM mosquitoes, the authors focused on a unique lectin isolated from the sea cucumber, which has both hemolytic and cytotoxic activities, as an anti-parasite effector molecule. A transgenic mosquito expressing the lectin effectively caused erythrocyte lysis in the midgut after ingestion of an infectious blood meal and severely impaired parasite development. This laboratory-acquired finding may provide significant implications for future malaria control using GM mosquitoes refractory to the parasites.


Shigeto Yoshida, Yohei Shimada, Daisuke Kondoh, Yoshiaki Kouzuma, Anil K. Ghosh, Marcelo Jacobs-Lorena, Robert E. Sinden. (2007) Hemolytic C-Type Lectin CEL-III from Sea Cucumber Expressed in Transgenic Mosquitoes Impairs Malaria Parasite Development. PLoS Pathogens Vol. 3, No. 12, e192 doi:10.1371/journal.ppat.0030192. [LINK]

Comments

  1. #1 Martin R
    December 21, 2007

    So the idea is to, one day, replace all wild populations of Anopheles mosquitos with a transgenic strain? Doesn’t sound realistic to me.

  2. #2 David Grantd
    December 22, 2007

    Maybe not completely unrealistic. Female mosquitoes mate only once. If large numbers of males homozygous for the malaria-inhibiting gene were released, it might be possible to ‘push’ the frequency of that gene up in the wild population.
    A similar strategy has eradicated screwworms from most of North America. Those are flies whose larvae can feed on live flesh, as opposed to housefly larvae (maggots) that can only eat dead stuff. Screwworm larvae infest wounds of livestock, killing a few and sapping the strength of a lot of them. The extermination program releases sterile adult males (I think they’re called horseflies and they look like a big house fly). They grow them and sterilize them with radiation. Every female that mates with a sterile male is effectively sterilized. They’ve even managed to breed extra sexy males, that mate with more females than the wild type males.
    The eradication program eliminated screwworms from the United States in 1966 (Reference: http://sanjose.usembassy.gov/screwwrm.html ) and was continued southward. Currently sterile flies are being released in Costa Rica, so I assume the ‘eradication frontier’ has been pushed south past most of Central America.