Study suggests genetic modifications could interfere with insect transmission of malaria

Brussels, 31 Jul 2006

Scientists from the UK and the US have made a major breakthrough in understanding the genetics of the insect parasite responsible for the spread of diseases such as malaria.

Wolbachia bacteria are parasites that infect as many as 80 per cent of the world's insects. They manipulate reproduction in their hosts in order to improve their own transmission. For example, in the fruit fly and mosquito, the Wolbachia alter the sperm of infected males in order to prevent them from reproducing with uninfected females. As Wolbachia is maternally transmitted, the infection is spread rapidly - infected females can successfully mate with any male, whereas uninfected females are restricted to uninfected males.

Malaria is one of the planet's deadliest diseases and one of the leading causes of illness and death in the developing world. According to the World Health Organization (WHO) there are 300 to 500 million clinical cases of malaria each year, resulting in 1.5 to 2.7 million deaths. If scientists could control the transmission of infection between mosquitoes, they would succeed in significantly reducing the spread of malaria.

Many researchers have been investigating the possibility of control strategies that use genetically modified (GM) Wolbachia. The GM parasite would carry genes making their mosquito hosts unable to transmit the plasmodium parasite that causes malaria. For the first time, scientists from the University of Bath in the UK and the University of Chicago in the US have identified two of the genes that Wolbachia manipulates when it infects the fruit fly Drosophila simulans.

'This is a major breakthrough in our understanding of the genetic basis of Wolbachia infection,' said Dr Ben Heath from the University of Bath. 'Part of the problem in studying Wolbachia is that it lives inside the cells of its host insect and cannot effectively be studied on its own because it needs the cellular machinery and materials it gets from its host to survive. Another difficulty is that the changes it makes in the development of sperm are so subtle that they can be difficult to trace,' he explains.

The UK-US team compared the genes that were being expressed in infected and uninfected male fruit flies. By subtracting one from the other, they were left with the genes that were being expressed as a result of the Wolbachia infection. One of the genes identified, known as 'zipper', is well known to scientists but had not been associated with Wolbachia infection.

The team worked with transgenic flies, which express the zipper gene more when warmed up slightly during their development. The researchers were thus able to mimic the effect of Wolbachia in fruit flies that do not carry the bacteria.

'The zipper gene identified by the scientists also interacts with a second gene called Igl, which is responsible for polarity within the cell and this becomes important when a cell divides into two different cells, such as when stem cells develop into sperm,' explains Dr Tim Karr, also from the University of Bath.

'By affecting the balance between these genes, it appears Wolbachia can promote cytoplasmic incompatibility by modifying the sperm of infected males. This prevents the sperm from being compatible with any egg from a female not infected with Wolbachia and results in sterility.

'However, when infected males mate with infected females, the Wolbachia in the egg finds a way of correcting the modification to sperm and allows fertilisation and normal development to continue.'

The researchers are now looking at mechanisms in other insect species, which have different levels of cytoplasmic incompatibility.

CORDIS RTD-NEWS/© European Communities, 2006
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