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
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