Genetically Modified Fungus Could Help Fight Malaria, Say Scientists

University of Westminster scientists have developed genetically modified fungi that can kill human malaria parasites in mosquitoes.

Research by Professor Angray Kang in the School of Life Sciences at the University of Westminster, Antibody Technology Group (ATG), has contributed to a significant breakthrough in the effort to control malaria by developing genetically modified fungi that kill human malaria parasites in mosquitoes.

Metarhizium anisopliae, a fungus found in soils throughout the world infects adult mosquitoes through the cuticle. This 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 says: “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, i.e. 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 fungi 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.

Other malaria experts aren’t so sure the lab results can be duplicated in the real world. Quoted in an AP story, Janet Hemingway, director of the Liverpool School of Tropical Medicine said, “It’s a neat scientific idea, but there are questions about (the mutated fungus’s) stability and formulation. She added that the fungus would have to survive months of shipping, as well as survive on the bednets for months after application

Sources: University of Westminster; NPR (AP).

Liverpool School of Tropical Medicine Launches AvecNet Collaborative Project to Fight Spread of Malaria

The Liverpool School of Tropical Medicine (LSTM) has launched a collaborative project to develop and evaluate new tools to control the spread of malaria in Africa. AvecNet is a five year, €12 million project involving sixteen partners in Africa and Europe, funded by the European Union’s Seventh Framework programme.

Because malaria is transmitted by mosquitoes, their effective control is essential to combating the disease. Wide scale use of insecticides on bednets and in interior spraying programmes has dramatically reduced transmission but continued success is dependent on a very limited range of insecticides and other tools.

AvecNet aims to secure the continued effectiveness of these methods into the future by developing and evaluating new insecticides and techniques that will overcome the growing threat of insecticide resistance, as well as designing new tools and interventions to target the mosquitoes that currently evade these control methods. The project also aims to increase existing knowledge about the biology and behaviour of mosquitoes to enable more effective control as urbanisation and other environmental factors alter the balance in this continuing fight against an evolving and formidable opponent.

Dr Hilary Ranson, Head of the Vector Group at LSTM and leader of AvecNet, said: “We need to secure the viability of existing malaria control programmes and expand their scope and reach by developing new methods and tools based upon a vastly increased understanding of how mosquitoes behave and react in different environments.

“We will also rigorously field test existing and prototype tools and techniques to both inform their further development and refinement and to add to the knowledge base from which we can develop further tools and interventions.

“By increasing research capacity in Africa and Europe and uniting people with skills in lots of different fields we are going to generate the momentum to achieve what we hope will be a number of significant breakthroughs in malaria control.”

Source: Liverpool School of Tropical Medicine