Researchers have identified a gene in mosquitoes that
helps the insects to fight off infection by the Plasmodium
parasite, which causes malaria in humans.
Anopheles mosquitoes transmit the malaria parasite to
nearly 550 million people worldwide each year with these
cases resulting in more than 2 million deaths annually. The
protective gene was identified in a study conducted by a
team of investigators from the Johns Hopkins Bloomberg
School of Public Health's
Malaria
Research Institute, the Imperial College of London and
the University of Texas Medical Branch. It was published
[the week of Oct. 24] in the Online Early Edition of the
Proceedings of the National Academy of Sciences.
The malaria-causing Plasmodium has a complex life
cycle. Mosquitoes become infected with the parasite when
they draw blood from humans who have malaria. As the
parasite matures, it moves from the mosquito's midgut to
its salivary glands. Once in the salivary glands, the
Plasmodium can be injected into another human when the
mosquito feeds again.
In the study, the researchers determined that the
SPRN6 gene, which is normally switched off in Anopheles
stephensi and Anopheles gambiae mosquitoes, is switched on
when they are infected with the malaria parasite. To
determine the function of SPRN6, the researchers
deactivated the gene in the mosquitoes through a process
called RNA interference. They observed that the number of
parasites that developed in Anopheles stephensi mosquitoes
increased threefold when the gene was knocked out. In
Anopheles gambiae mosquitoes, removing the SPRN6 gene
delayed the process of parasite lysis, whereby the mosquito
rids itself of the parasite.
"This study furthers our knowledge of the
malaria-parasite lysis in mosquitoes. It may help provide
better tools for controlling the disease in the future,"
said lead author Eappen G. Abraham, research associate in
the
Department of Molecular Microbiology and Immunology and
the Malaria Research Institute at the Bloomberg School of
Public Health.
"These results provided new insights into how the
mosquito defends itself from the malaria parasite," said
co-author Marcelo Jacobs-Lorena, a professor in the
Department of Molecular Microbiology and Immunology and the
Malaria Research Institute at the Bloomberg School of
Public Health. "More research is needed, but we plan to
apply this knowledge in the development of new approaches
to control the disease."
Abraham and Jacobs-Lorena are developing a transgenic
mosquito in which the SPRN6 gene is permanently switched
on, in an effort to create a mosquito that would be immune
to the Plasmodium parasite. They believe that such a
mosquito could help disrupt the transmission of malaria to
humans.
The study was written by Abraham, Anil Ghosh and
Jacobs-Lorena, of the Bloomberg School of Public Health;
Sofia Pinto, Aidan Budd, Fotis C. Kafatos and Kristen
Michel, of the European Molecular Biology Laboratory,
Heidelberg, Germany, and the Imperial College of London;
and Dana L. Vanlandingham and Stephen Higgs, of the
Department of Pathology at the University of Texas Medical
Branch.
Funding was provided by the European Molecular Biology
Laboratory and grants from the National Institutes of
Health, the Defense Advanced Research Planning Agency, the
Chemical Biological and Radiological Sciences and
Technology Defense Branch of the Naval Surface Center, and
the German Research Foundation.
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