Roughly half the world's population
still lives in areas at risk of malaria transmission. Even in the
United States, 1500 cases of malaria are reported annually on average.
One way to curtail the spread of malaria and other mosquito-borne
diseases is to decrease the number of mosquitoes.
Now a five-year, $1.86 million grant to the University of California,
Riverside from the National
Institute of Allergy and Infectious Diseases
entomologists come closer to realizing this goal, potentially benefiting
millions of people worldwide.
, the principal investigator of the renewal grant, and
colleagues will use the new funding to continue their work on developing
genetically engineered bacteria for killing mosquitoes - specifically,
"Most new tactics today that use genetic engineering technology target a
single species of mosquito," said Federici, a distinguished professor
. "Our solution,
however, is aimed at an enormous number of mosquito species, including
those responsible for malaria, West Nile, dengue fever and filariasis."
Certain bacteria bear proteins that are highly toxic to only mosquitoes.
In collaboration with industry, Federici's lab already has examined two
different strains of such bacteria - Bacillus sphaericus
and Bacillus thuringiensis
(Bt) - and engineered their
mosquito-killing properties into a single new bacterial strain.
"This recombinant Bt/Bs strain is about ten times more effective than
either one of the strains we used to combine the properties, and it is
environmentally safe," he said. "Further, our recombinant is far more
effective than bacterial strains used in commercially available products
Most available products exist in the form of a dried powder or liquid
suspension in which the bacterium remains active. Widely used on
vegetable crops, they are either sprayed from airplanes or hand-held
sprayers. When mosquito larvae ingest the product, it destroys their
stomachs and the larvae die within two hours. The proteins in the
bacterium that kill the larvae are specific for mosquito larvae,
attacking only these and certain other flies, nothing else.
Federici explained that his lab was able to accelerate the development
of a recombinant bacterial strain by invoking genetic engineering into
"It would probably be impossible to do what we did with just normal
selection," he said. "It is far easier to take a gene from one
bacterium and insert it into the DNA of another bacterium. Still, it
took us ten years to get to this stage. We spent a good amount of time
doing basic research to understand what controls the synthesis of
To make the recombinant bacteria, Federici's lab constructed "plasmids" -
small, circular pieces of DNA - using techniques developed in his lab
as well as by other molecular biologists. The researchers cloned the
genes coding for mosquito-killing bacteria from the two bacterial
species, Bt and Bs, and then inserted them into the same new plasmid
they constructed using genetic engineering techniques. They engineered
the genes so that they would produce larger amounts of the desirable
proteins. Finally, they injected the plasmid into a bacterium cell,
rendering it recombinant (that is, containing genes from two or more
Researchers in Federici's lab will use the grant to continue doing basic
research on how the bacterium synthesizes the proteins. They also will
explore fundamental questions about how the bacterium controls
synthesis of these mosquito-killing proteins, as well as why these
proteins are so specific for mosquitoes.
"Our work has implications for controlling many vector-borne diseases
worldwide - filariasis in India, malaria in Africa, India, and Central
and South America, and various viral diseases transmitted by mosquitoes
around the world," Federici said. "Our recombinants are very good at
mosquitoes that occur in Brazil, India, Thailand,
China and Mexico. In preliminary field tests, we found that our
recombinants kill 95-100 percent of the mosquitoes."
According to Federici, another significant advantage of using
recombinant bacteria is that they come with built-in resistance
"Mosquitoes can become resistant to bacterial control agents," he
explained. "Work in my lab has shown that it is possible to delay the
evolution of mosquito resistance because this resistance takes much
longer to evolve when recombinants are involved.
"Our preliminary efficacy data shows that our method works. We have a
few more hurdles to jump over. But if all goes according to plan, we
could have a product commercially available in 3-5 years. Certainly,
our industry partners are eager to move forward."
The grant will support graduate students, specialists and postdoctoral
researchers. Federici already is joined in the research by UCR's
Margaret Wirth, a staff research associate in the Department of
Entomology, and Mercedes Diaz-Mendoza, a postdoctoral researcher working
in Federici's lab; and Dennis Bideshi and Hyun-Woo Park of California
Baptist University, Riverside. Both Bideshi and Park also hold
appointments as specialists in UCR's Department of Entomology.
In particular, Wirth will focus on the evolution of insecticide
resistance to microbial toxins, the genetic basis of this resistance and
evaluating the bacterial insecticides.
"We will also determine whether exposure to sublethal concentrations of
microbial insecticides affects the adult longevity of female vector
mosquitoes," said Wirth, who works in Federici's lab as well as the lab
, a professor of entomology.
Wirth explained that adult female mosquito longevity is the primary
factor influencing the risk for disease transmission.
"This is because females must take a blood meal from an infected host,
lay eggs, and survive long enough to take a second blood meal in order
to transmit the disease agent," she said. "If adult female longevity is
reduced in survivors of larval exposure to bacterial insecticides, then
these can reduce the overall numbers of mosquitoes as well as the rate
of disease transmission."