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By Alex Crees
Researchers report they have found a way to kill malaria in mosquitoes by genetically modifying a bacterium commonly found in the insect’s mid-gut, according to a new study.
The bacterium, called Pantoea agglomerans, can be modified to secrete proteins that are toxic to the malaria parasite, but are not harmful to humans or the mosquito itself. In fact, the bacterium is so specific to targeting malaria that it does not even affect other bacteria in the mosquito’s gut, according to the researchers from Johns Hopkins Malaria Research Institute, who conducted the study.
The bacterium is genetically engineered to attack malaria in multiple ways.
“There are not one, but several anti-malaria compounds the bacterium secretes,” explained Dr. Marcelo Jacobs-Lorena, senior author of the study and a professor at the Johns Hopkins Bloomberg School of Public Health. “Each acts by a different mechanism and makes it much more difficult for the parasite to develop a resistance to it.”
One of the compounds secreted by the bacteria, for example, inserts itself into the membrane of malaria parasite, essentially poking holes in the parasite’s protective outer layer and causing it to ‘leak out’ and die. Another one of the compounds binds itself to a crucial protein the parasite needs to survive, thus blocking the parasite from the taking advantage of the protein.
According to the researchers, the bacterium successfully inhibited the development of the deadliest human malaria parasite, known as Plasmodium falciparum, and the rodent malaria parasite, Plasmodium berghei, by up to 98 percent in a small preliminary study. The bacterium reduced the prevalence of malaria among the mosquitoes by up to 84 percent.
Past approaches to fighting malaria in mosquitoes focused around genetically modifying the insects themselves to resist malaria. However, scientists found – while successful in the lab – it was much more difficult to spread the genetic changes in nature.
“We changed the strategy, taking advantage of the fact that mosquitoes, like humans, carry big population of bacteria in their guts,” Jacobs-Lorena said. “We took one of bacteria and engineered it to produce anti-malaria proteins. We re-introduced it back into the mosquitoes and found it works quite well.”
The reason this approach cannot be taken in humans, he added, is that while mosquitoes carry malaria in their guts, malaria nearly exclusively spreads through the bloodstream to the liver in humans – completely bypassing the gut.
Ethical concerns
Among mosquitoes, Jacobs-Lorena believes the bacterium can spread rapidly, through relatively low-cost, low-tech means. By simply soaking cotton balls in sugar and the bacteria, then placing the cotton balls in clay jars where mosquitoes tend to dwell, the insects feed on the cotton balls and contract the bacteria.
The major challenge instead, according to Jacobs-Lorena, will likely be the regulatory and ethical issues associated with releasing genetically modified organisms in nature. The researchers will need approval from both regulatory agencies and communities before conducting trials in the field.
“It may take quite a bit of effort,” Jacobs-Lorena said. “People are predisposed against genetically modified foods and plants. Imagine what kind of challenges we’ll have with this. The advantage in this case we are talking about saving lives, rather than growing food more efficiently or economically.”
First, Jacobs-Lorena and his team plan to conduct semi-field studies with mosquitoes in greenhouses, to show ‘proof of principle’ that the bacterium can work similarly in an outside environment as does in a lab, without any problems.
The researchers also plan to work further with another bacterium, known as serratia, which may potentially be more effective than Pantoea agglomerans. The researchers found serratia appears to grow faster in the mosquito’s gut and populates the ovaries as well – meaning it can be passed from parent to offspring.
“It was a chance discovery,” Jacobs-Lorena said, adding that work with the second bacterium is still in its early stages.
However, Jacobs-Lorena insisted that regardless of regulatory decisions or potential, neither bacteria would be the “a magic bullet” for malaria, which kills approximately 800,000 people each year.
“We cannot forget about other measures,” he said. “The way I envision this is we have restricted ways to fight malaria – drugs for humans, insecticide for mosquitoes – and because the number of malaria cases are so high, these have not been efficient. I envision this as an additional tool to complement existing measures and make the fight more effective.”
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