Genetically modified fungus is new weapon in fight against malaria

2 March 2011

A genetically modified fungus that kills the human malaria parasite in mosquitoes has been developed by the Antibody Technology Group (ATG) in the School of Life Sciences at the University of Westminster, London.

This major breakthrough has been heralded as a significant development in the battle against malaria which kills almost a million people around the world each year.

The fungus, Metarhizium anisopliae, is found in soils throughout the world and infects adult mosquitoes through the cuticle. The fungus was genetically modified by the research group and used to infect malaria-carrying mosquitoes. The fungus killed the malaria parasite in the mosquitoes, preventing it from being passed onto humans.

Professor Angray Kang of ATG said: “This is a major development in the battle against malaria. Efforts to control the disease are normally hampered by an increased resistance of parasites and mosquitoes to drugs and insecticides respectively.

"This will be a crucial part of the solution of eradicating malaria, which was an ambitious goal set by the Bill and Melinda Gates Foundation. It is important to understand that we do not treat people using this method, but cure the mosquito before it has had a chance to infect a person. This innovative approach could also offer a solution for controlling other devastating vector-borne diseases.”

Upon contact with the mosquito the fungus immediately bores in through the cuticle. As the fungus eats away at the inside of the mosquito, it multiplies and occupies their circulatory system (hemolymph), eventually killing the insect.

This is the same fluid that the malaria parasite has to navigate through to reach the salivary glands and to become infectious. By genetically engineering the fungus to release anti-malarial agents into the hemolymph, it is possible to prevent the malaria parasites from reaching its infectious destination.

Since the fungal spores are taken up by contact, they can be applied to surfaces in the same way insecticides are applied, ie on walls, cloth ceilings and bednets by spraying or at baited stations. The idea of this new technique is to break the cycle of mosquito’s transmitting the disease to humans, it can become infected with lethal human parasite Plasmodium falciparum, but this cannot then be further transmitted to humans.

ATG has focussed on creating the antibody-based molecules to target the disease agent and have pursued an approach called paratransgenesis to get the antibodies inside insects. This technique involves modifying the bacteria or fungus which can be used to express the anti-parasite antibodies in the insects using a ‘Trojan Horse’ approach.

Working alongside Ravi Durvasula, Professor Kang was the first to show that such an innovative approach was feasible in bacteria, and now, working with Professor Ray St Leger, it has been applied to a fungus. To allow Metarhizium anisopliae to combat malaria in mosquitoes with advanced malaria infections, ATG designed a form of a human monoclonal antibody PfNPNA-1 that targets the surface of the parasite stage that is released into the hemolymph which then migrates to and invades the salivary glands.

The PfNPNA-1 causes the P. falciparum sporozoites to clump as they travel through the hemolymph preventing them from reaching the salivary glands, and therefore halting the spread of malaria.