April 10, 2012, 9:52 a.m.
by Christen Brownlee
In the centuries-long battle against malaria, people have tried a variety of ways to fight Plasmodium, the microscopic parasite responsible for the disease.
They’ve strung up bed nets, sprayed insecticides and used repellents to prevent infectious bites from Plasmodium’s mosquito hosts, and they’ve developed assorted medications that poison this parasite inside humans. Soon, scientists might have one more weapon to add to the anti-malarial arsenal: a microscopic foe. Researchers including George Dimopoulos, PhD, and Jason Rasgon, PhD, both associate professors in Molecular Microbiology and Immunology, are taking aim at Plasmodium using bacteria.
Dimopoulos’ strategy relies on native bacteria that live in a mosquito’s gut—much like the endemic bacteria that line people’s intestines. In 1999, his lab was one of the first to discover that these bacteria can activate the mosquito’s immune system in a way that kills Plasmodium. However, it was unclear then whether their results were relevant only to mosquitoes living under lab conditions, which may behave differently from mosquitoes in the wild.
In new research, Dimopoulos and his colleagues sampled bacteria from mosquitoes field-caught near the Johns Hopkins Malaria Research Institute site in Macha, Zambia. They discovered a species of Enterobacter bacteria that thwarted growth of the parasite by up to 99 percent, rendering most mosquitoes unable to transmit malaria.
Surprisingly, these bacteria work their magic without stirring up the mosquito’s immune system. In a May 13 Science article, Dimopoulos’ team discovered that this Enterobacter species spews out free radicals, which effectively block Plasmodium’s development. (Free radicals are highly reactive molecules that can cause tissue damage.) Eventually, Dimopoulos says, people might feed this bacterium to mosquitoes—perhaps mixed in artificial nectar, sprayed on vegetation—to kill the parasite before mosquitoes can transmit it to people.
“This approach would be low-cost, ecologically friendly and logistically simple,” Dimopoulos says. “It could be another great weapon in the fight against malaria.”
Rasgon’s approach takes a different tack. His lab works on Wolbachia, a group of bacteria that infect many insect species—but not typically Anopheles, the mosquito genus that carries malaria. For the past decade, Rasgon has been working on goading Wolbachia to infect Anopheles, inspired by work on other mosquito species showing that the bacterium can knock out pathogens that infect people, such as dengue. In a new study, Rasgon’s team showed for the first time that artificially infecting Anopheles with Wolbachia by injecting the bacterium into the insects significantly reduces Plasmodium loads. Additionally, a particular strain of Wolbachia proved fatal to the mosquitoes when they fed on a blood meal, potentially also from production of free radicals.
Enterobacter “could be another great weapon in the fight against malaria.” —George Dimopoulos
If researchers can figure out how to more readily infect Anopheles with the bacterium, both effects could be useful to fight malaria, Rasgon notes, either through clearing the mosquitoes of the parasite or killing off mosquitoes altogether.
Such interactions between bacteria and disease-causing parasites have occurred from time immemorial. So, why are researchers just taking advantage of them now? It’s all in the technology, says Serap Aksoy, PhD, a Yale researcher who studies native bacteria in tsetse flies and how these might fight the parasite responsible for the African sleeping sickness these flies transmit.
“Many bacteria, often symbiotic in nature, cannot be cultured in the laboratory,” she says, “so researchers are only becoming aware of these microbes and their potential after PCR-based methods and genomic sequencing technologies became available. In general, we now have a greater appreciation of the extent of influences microbes have on their host’s biology.”
Gaining a better understanding of these newly discovered microbes won’t be the magic bullet against malaria, Aksoy says, but it could play an important part in the battle. “The toolbox against this disease is still so limited,” she says, “so any advance is well worth trying.”