Genetically Modified Fungi Prevent Parasite Development in Malaria Mosquitoes

spores of Metarhizium anisopliae in an oil formulation germinating on locust cuticle

K. Amponsah-Manager

A team of scientists in the UK and US have genetically modified a fungus that prevents the development of malaria-causing parasites in the mosquitoes.  The study which has been published in the journal Science showed that the fungus can eliminate up to 90% of the parasite in the vector that carry it, the female anopheles mosquito.

The scientists inserted the genes of human antibodies or scorpion toxins into a fungus called Metarhizium anisopliae and infected mosquitoes with the fungus. This conferred onto mosquitoes infected with the fungus the ability to block the development of malaria-causing parasites in mosquitoes.

The female Anopheles mosquitoes are the vectors for the malaria parasite, Plasmodium, which develop inside the body of mosquitoes. The mosquito simply helps to shuttle the parasite between infected person and healthy people and therefore the ability to deprive the parasite of its taxi service is key to fighting the illness.

Due to the environmental hazards of using pesticides to fight the malaria mosquitoes and the development of resistance to many anti-malarial products, recent years scientists have focused their attention on finding natural and environmental friendly methods to fight the disease. The fungus Metarhizium anisopliae naturally kills mosquitoes but unlike parasites, it takes day to accomplish that. The advantage of the Fungi’s patience is that because the mosquitoes can mate and do their usual chores, they have less reason to develop resistance.

Results of the study showed that malaria parasite survived in the salivary glands of 25 percent of the mosquitoes sprayed with the genetically modified organism, compared to 87 percent of those sprayed with an unmodified strain of the fungus, and to 94 percent of those that were not sprayed at all.

The good news from the study is the possibility that spraying malaria-transmitting mosquitoes with the genetically-modified fungus, also known as transgenic fungus, could one day become a feasible method to significantly reduce the transmission of the disease to humans.

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Ingestion of ‘modified’ starch could be a new malaria vaccine strategy

Electron microscope image showing starch (white shell) containing a peptide of Plasmodium (black dots of gold particles) coupled with the GBSS of the green algae Chlamydomona. Credit:Stan Tomavo, CNRS

There is no efficient vaccine against malaria, although nasal and oral vaccination seems to be the most promising and suitable solution in countries where the parasite Plasmodium, which causes the disease, is rife. Researchers from two laboratories in northern France have successfully vaccinated and protected mice by feeding them starch derived from green algae and genetically modified to carry vaccine proteins. These encouraging results, which make it possible to envisage a simple and safe vaccination for children in countries at risk, are available online, on the scientific journal PloS One’s website.

According to the WHO, malaria affects approximately 300 to 500 million people worldwide and kills one million each year, mostly young children. Insecticide-resistant carrying the disease and multi-drug resistant are on the increase. In this context, the development of a vaccine that alleviates symptoms and reduces mortality would be a valuable new tool in the fight against malaria. Researchers aim to test the efficacy of vaccine candidates among proteins that allow the parasite to penetrate host cells and infect them, in order to devise the best strategy for vaccine delivery.

Researchers from the Centre d’Infection et d’Immunité de Lille and the Unité de Glycobiologie Structurale et Fonctionnelle have developed a new vaccine strategy based on the ingestion of genetically modified starch. They used antigens that have shown their efficacy in “conventional” vaccinations as vaccine candidates. They fused these antigens to an enzyme (GBSS) in a starch granule from the , Chlamydomonas reinhardtii. This enzyme has the particularity of functioning inside the starch granule and of being protected, along with the antigens grafted to it, against degradation by other enzymes. In this way, the researchers were able to produce several murine and human antigens of Plasmodium within starch grains. These grains were then ingested by mice inoculated with the parasite. The researchers demonstrated that the mice were vaccinated by the starch grains, which significantly protected them against infection.

Starch is the insoluble and semi-crystalline polysaccharide that is the most commonly found in photosynthetic organisms. A starch grain can easily be produced from a plant extract and purified, in large quantities. It has a very stable structure and can be stored for months with no particular precaution, even if it undergoes temperature variations. It is easily assimilated through digestion and has a major ecological and financial interest, with very low production costs.

The starch of edible plants could be transformed in the same way as that of the algae Chlamydomonas reinhardtii. Researchers are thus looking at the possibility of using starch from multi-cellular algae used in Africa as a food supplement, but also from maize and potatoes. Administered to children under 3 years of age, who are at high-risk of malaria-related mortality, such plants could be both a food source and a vaccine. This strategy would allow simple vaccination, avoid storage problems and syringes, and thus eliminate potential HIV contamination.

The strategy based on the ingestion of genetically modified starch is protected by a patent.

The researchers now plan to test the efficacy of various Plasmodium antigens and determine whether such strategy can be applied to humans by verifying it has no side effects.

physorg.com
More information: PloS One, 15 December 2010: http://www.plosone … pone.0015424 .
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A Breakthrough in Malaria Research

Scientists from Scotland have reported a major breakthrough  in fight against malaria.

The team from Edinburgh University in collaboration with  a team in Portugal  have discovered a gene that offers the drug resistance trait to the parasite. Drug-resistant plasmodium falciparum parasites are a major hindrance in the battle against the deadly disease. Chloroquine, the most commonly prescribed medicine against malaria has lost its effectiveness due to the proliferation of chloroquine resistant parasites.

Scientists think this is a  major development in malaria research. Malarial kills one to three million people annually, mostly children. These findings may pave a way for a new class of anti-malarials.

The study has been published in Biomedical Central (Sept 2010)

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