UF Study: Key To Controlling Disease-Bearing Mosquitoes May Be NATs

January 20, 2005

GAINESVILLE, Fla. — A new University of Florida study suggests a novel way to control populations of disease-bearing mosquitoes: target the way those insect cells absorb nutrients from their diet.

The UF researchers have identified a group of molecules in the gut of a mosquito that deliver essential amino acids to the mosquito’s cells. Because those nutrient amino acid transporters, or NATs, are unique to a species, blocking them won’t affect the delivery of nutrients to other species such as humans.

Their findings, which appear in the current issue of the Proceedings of the National Academy of Sciences, could lead to new ways of controlling disease-carrying species and agricultural pests.

“This is a very directed way to get a new mosquitocide,” said William Harvey, a UF professor of physiology and functional genomics and a co-author of the study. “What makes this so exciting is that there are only insect transporters in that cluster (of transporters). The beautiful thing is there aren’t any human transporters there at all, no birds or anything else — so it won’t do anything to the environment.”

Many of the most dangerous infectious diseases in the world are carried by mosquitoes, including West Nile virus, encephalitis, yellow fever, dengue fever and malaria. To reduce populations of disease-bearing mosquitoes, scientists have developed insecticides that generally act on the mosquito’s nervous system, Harvey said.

“But when they do that, the human nervous system is very similar,” he said. “So there’s always a problem that you can kill the insects but also people.”

All multicellular species, from humans to rodents to mosquitoes, share a genetically similar group of molecules called neurotransmitter transporters, said Dmitri Boudko, an assistant professor at UF’s Whitney Laboratory for Marine Bioscience and lead author of the paper. Those transporters target the nervous system and regulate levels of chemicals such as dopamine.

Similarly, amino acids require transporters to cross cell membranes so they can be absorbed into cells. However, unlike neurotransmitter transporters, amino acid transporters evolved differently from species to species, allowing organisms to adapt to environmental changes. Because amino acid transporters are genetically distinct, it’s possible to affect nutrient uptake in some species but not others. Several amino acids are essential to an organism’s survival, Boudko said.

“We know that the lack of those essential amino acids in the diet will interrupt development and dramatically increase mortality in mosquito larval populations,” he said.

If the transporters don’t bind to the amino acids, the mechanism breaks down – and that can spell big trouble for a species. Therefore, any interference with the function of these transporters, either chemically or on a molecular level, could potentially cause a deficiency in the amino acid it is supposed to transport – a kind of dietary deprivation.

Now that they have isolated those distinct nutrient amino acid transporters in insects, the UF team is seeking ways to take advantage of that genetic individuality to design a method to selectively control pest species. The researchers have applied for a patent for their discovery, covering both their method of isolating the nutrient amino acid transporters and the idea to inhibit them.

“There is really a big need for something powerful but cheap,” Harvey said. “The broad project is to first use the existing mosquitocides and technologies, and just improve them. Then we can go from helping people who are using existing methods to ours — the ideal solution in the long run.”

DDT is a classic example of an inexpensive, powerful insecticide that is also dangerous to humans. More recently, however, scientists have developed other insecticides that affect only insects, such as toxins derived from a soil bacterium — yet those can be prohibitively expensive to manufacture.

Other ways to combat insect-borne disease include vaccines and even genetically engineered mosquitoes that are bad at transmitting diseases. However, both of those methods only focus on one disease at a time.

Finding such a novel, and environmentally friendly, way to manage these serious diseases is crucial, said Robert Novak, a professor of medical entomology at the University of Illinois.

“(The UF team is) looking at the fundamental mechanisms of insect physiology and ecology and using them in a unique fashion,” Novak said. “It really goes back to what does the insect require, what is the motor that really runs these animals? And by better understanding that motor, can we make things that can really suppress disease in an ecological framework?

“This is really very important because in today’s world we are very concerned about the environmental impact,” he said. “A lot of the weapons we once had are not available to us because of the harshness to the environment or to humans.”