Fighting Malaria By Modifying Friendly Bacteria In Mosquito Gut

Date: Jul-17-2012By genetically modifying gut bacteria in the malaria mosquito, US researchers have found a potentially powerful way to fight malaria. The
modified "friendly" bacteria, which live in the midgut of the mosquito alongside the malaria parasite, produce toxins that are deadly to the parasite but do not
harm humans or mosquitoes.

Writing in a paper published online on 16 July in PNAS, the researchers suggest their findings provide a "foundation for the use of genetically modified
symbiotic bacteria as a powerful tool to combat malaria".

Senior author Marcelo Jacobs-Lorena, a professor with Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, told the press:

"In the past, we worked to genetically modify the mosquito to resist malaria, but genetic modification of bacteria is a simpler approach."

The researchers already knew that the most vulnerable stage of development of Plasmodium, the mosquito parasite that causes malaria, occurs in the
lumen of the midgut in the mosquito, an environment shared with symbiotic or "friendly" bacteria.

Also, from previous work, Jacobs-Lorena had already established that one of the symbiotic bacteria, Pantoea agglomerans, can be genetically modified
to secrete "antimalaria effector molecules" that are toxic to the malaria parasite.

In this study, they describe how they used the "Escherichia coli hemolysin A secretion system" to make Pantoea agglomerans secrete a range of
anti-Plasmodium effector molecules.

The engineered gut bacteria strains "inhibited development of the human malaria parasite Plasmodium falciparum and rodent malaria parasite
Plasmodium berghei by up to 98%", they write.

They also found the proportion of parasite-carrying mosquitoes (prevalence) fell by up to 84% for two of the effector molecules: scorpine and (EPIP)
4.

Every year more than 800,000 people, most of them children, die from malaria.

The good news is that since 2000, global malaria deaths have been reduced by more than 26%, with 1.1 million children's lives saved in Africa.

Also, since the millenium, 8 African countries have cut malaria incidence by more than 50%, and 25 countries are on the path to eliminating malaria
altogether.

One reason for progress is that funding for fighting the disease rose from $35million in 2000 to almost $1.5billion in 2009: a fortyfold increase.

The battle against malaria has to be fought on a number of fronts: insect repellent and bed nets can help prevent transmission from mosquitoes to humans, but
work like that of Jacobs-Lorena and colleagues helps to find ways to control malaria one step earlier by eliminating infection within the mosquito
itself.

In May 2011, another team from Johns Hopkins University reported identifying a class of
naturally occurring bacteria that can strongly inhibit malaria parasites in mosquitoes. They found the presence of Enterobacter reduced various
developmental stages of P. falciparum, including the stage that is transmitted to humans through a mosquito bite, were reduced by 98 to
99%.

Written by Catharine Paddock PhD

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