By David F.
November 26, 2001
The mosquito may be nature's most effective
bioterrorist, accounting for millions of deaths each year. But the
end of its eons-long reign of terror may be in sight. Scientists
have begun to apply the power of genomics and molecular biology
to understand how the mosquito detects the subtle chemical cues
that lead it to its targets.
mosquito is the most dangerous animal on the planet. It relies on
its sense of smell to find the source of its blood meals. So understanding
how its olfactory system works at the molecular level should suggest
new and novel ways to keep it from spreading catastrophic diseases,"
says Laurence J. Zwiebel, assistant professor of biological sciences
at Vanderbilt. His laboratory is the first to have identified the
genes that code for proteins, called odorant receptors, which are
a key part of the mosquito's olfactory system. These proteins extend
outside olfactory neurons and, when they come into contact with
specific chemicals in the form of odors, initiate the cascade of
electrochemical events that produce the sense of smell.
Writing in the Nov. 27 issue of the
online version of the Proceedings of the National Academy of Sciences,
Zwiebel and his colleagues at Vanderbilt, the University of Illinois,
Urbana-Champaign and Yale University report isolating four genes
from the genome of Anopheles gambiae - an African mosquito that
feeds primarily on humans and spreads malaria - that are extremely
similar to genes generally considered to code for odorant receptors
in the fruit fly Drosophila, which serves as a scientific model
for insects. The researchers also determined that these genes are
only expressed in the mosquito's antennae and maxillary palps, which
serve a role similar to the nose.
There is a general misconception that
mosquitoes pick prey based on the taste of their blood. Actually,
previous studies have shown that mosquitoes are primarily attracted
by body odor and other emissions such as carbon dioxide. "We all
produce a cloud of chemicals and mosquitoes can track the odor trail
that we leave for quite a distance," says Zwiebel. Many of these
chemical cues are created by the bacteria that cover our bodies.
Studies have shown that fewer mosquitoes attack a person after they
have taken a shower. If the person showers with anti-bacterial soap,
the number drops even further.
Despite the large evolutionary distance
between man and mosquito, at the molecular level both are equipped
with basically the same chemosensory system. "Ever since evolution
figured out how to sense different chemicals, it has kept the same
molecular switches and machinery. The system in your nose and my
nose recapitulates that found in insects," says Zwiebel.
The fact that the olfactory system
is so highly conserved helped the researchers identify the A. gambiae
odorant receptor genes. They found four potential genes by scanning
the six percent of the mosquito genome that was then available for
sequences that looked similar to odorant receptor genes found in
Drosophila. Once they identified the genes, they were able to determine
that all four were only expressed in the antennae and maxillary
palps that are part of its olfactory system and not in any other
tissues. In the fruit fly some 60 receptor genes are involved in
olfaction, so Zwiebel and his colleagues expect to find about the
same number in the mosquito.
Furthermore, the researchers were able
to show that one of the newly identified odorant receptors appears
to be associated with the blood feeding patterns of the female A.
gambiae. In mosquitoes, it is only the female that is responsible
for biting people and spreading disease. The female needs blood
to reproduce. Previous studies have found that for about 72 hours
after feeding, female mosquitoes don't respond as strongly to human
odors as they do normally. Suggestively, the Vanderbilt group found
that one of the new receptors is expressed only in female antennae
and exhibits decreased expression levels during this post-feeding
The researchers hope that these kinds
of discoveries will eventually suggest new and effective ways to
keep mosquitoes from preying on people that will be less poisonous
than the insecticide and repellent sprays now in common use. For
example, a compound might be found that reduces the mosquitoes'
response to human odors. "Of course, the obvious goal is to make
effective repellents. There is a widespread need for a good mosquito
repellent," says Zwiebel. There are other possible approaches as
well. If a potent mosquito attractant could be found, it could be
used to lure them into a container filled with a potent insecticide.
"Molecular biology provides a new arrow
in the quiver of both high and low tech methods that the World Health
Organization and other groups are using to combat this scourge,"
Vanderbilt University has filed for
a patent on the newly discovered genes because there is considerable
commercial interest. While malaria has been largely eliminated in
industrialized countries like the United States, there is still
considerable interest in mosquito repellant sprays, and recent outbreaks
of West Nile fever indicate that the threat of mosquito-borne diseases
cannot be ignored.
In addition, the highly conserved nature
of the olfactory system means that similar approaches are likely
to work in other insects that pose threats as agricultural pests.
So research of this sort may ultimately lead to ways to reduce insect
damage to crops and stored food, along with a number of other useful
In addition to Zwiebel, collaborators
on the study are A. Nicole Fox, a graduate student, and R. Jason
Pitts, a research associate, both in the Zwiebel laboratory, and
Hugh M. Robertson of the University of Illinois at Urbana-Champaign
and John Carlson at Yale University.
The research was funded by the World
Health Organization, the National Science Foundation and the National
Institutes of Health.
Dr. Laurence Zweibel's home page may
be found at