Researchers at the Johns Hopkins Malaria
Research Institute have identified, for the first
time, the molecular components that enable the
malaria-causing parasite Plasmodium to infect the
salivary glands of the Anopheles mosquito — a
critical and final stage for spreading malaria to
humans.
According to the researchers, saglin, a mosquito
salivary protein, is a receptor for the
Plasmodium protein thrombospondin-related anonymous
protein, known as TRAP. The two proteins bind
together to allow invasion of the salivary gland by
Plasmodium sporozoites, which can be transmitted
to a human when bitten by an infected mosquito. The
findings are published in the Jan. 16 edition of
PLoS Pathogens.
Through a series of experiments, the JHMRI researchers
found that saglin bound with the
artificial peptide SM1. The team then developed an antibody
to find a protein similar to SM1 that
existed naturally in the parasite, which they identified as
TRAP. To further prove the interaction
between saglin and TRAP, the team conducted experiments to
down-regulate, or switch off, saglin
expression, which greatly diminished salivary gland
invasion in the mosquito.
"This work is the culmination of a decade-long
research project in which peptide libraries were
used to understand the mechanisms that the parasite uses to
develop in its obligatory mosquito host,"
said Marcelo Jacobs-Lorena, an author of the study and a
professor in the Johns Hopkins Bloomberg
School of Public Health's W. Harry
Feinstone Department of Molecular Microbiology and
Immunology.
Co-author Nirbhay Kumar, also a professor in Molecular
Microbiology and Immunology, said,
"Identification of molecular recognition mechanisms between
the parasite and mosquito vector
provides novel targets for further investigation aimed at
interrupting malaria transmission." Using
different methods, Kumar and his colleagues had previously
identified the saglin protein and
suggested it could potentially be a sporozoite receptor.
Malaria is estimated to infect 300 million to 500
million people worldwide, resulting in more than
1 million deaths, each year. JHMRI was established in 2001
at the Bloomberg School to mount a broad
program of basic-science research to treat and control the
deadly disease.
Additional authors of the study are Anil K. Ghosh,
Martin Devenport, Deepa Jethwaney, Dario E.
Kalume, Akhilesh Pandey, Vernon E. Anderson and Ali A.
Sultan.
The research was supported by the National Institutes
of Health, the Johns Hopkins Malaria
Research Institute and the Bloomberg Family Foundation.
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