Researchers at the Johns Hopkins Malaria
Research Institute have identified a sugar in
mosquitoes that allows the malaria-causing parasite,
Plasmodium falciparum, to attach itself to the
mosquito's gut. Invasion of the midgut cell layer is an
essential stage in the parasite's life cycle and in
the transmission of malaria from mosquitoes to humans. By
reducing the level of the sugar, chondroitin
sulfate, in the mosquito, the researchers prevented 95
percent of the parasites in the mosquito from
attaching to the gut, thus blocking its development. The
study is published in the Sept. 10 online early
edition of Proceedings of the National Academy of
Sciences.
"This study provides significant new insights on how
the parasite develops in the mosquito,
complementing our earlier identification of another
parasite midgut receptor that is a target for a
transmission-blocking vaccine," said Marcelo Jacobs Lorena,
senior author of the study and a
professor in the Bloomberg School's W. Harry Feinstone Department
of Molecular Microbiology and
Immunology. "This line of research could lead to new
approaches for interfering with the spread of
this deadly disease."
To determine whether the parasite utilizes chondroitin
glycosaminoglycans to invade the
mosquito midgut cells, the researchers used a process known
as RNA interference to inhibit
production of a mosquito enzyme that is needed to produce
chondroitin sulfate. With the sugar
removed, parasite adhesion and midgut invasion were
substantially decreased.
"Our study highlights the importance of sugars in
parasite invasion of the mosquito gut.
Previously, this phenomenon was only observed during
parasite invasion of human tissues," said Rhoel R.
Dinglasan, lead author of the study and a postdoctoral
fellow with the Malaria Research Institute. "It
appears as if the parasite's use of sugars as a strategy
for cell invasion of tissues is similar in both
man and mosquito. This may be an Achilles' heel for the
parasite, opening up the possibility of
developing a vaccine that works against all stages of the
parasite's life cycle."
According to the researchers, many important questions
must still be answered to determine if
the glycosaminoglycan identified could be a potential
antigen for a transmission-blocking vaccine. In a
study published earlier this year in PNAS, the Malaria
Research Institute team identified a previously
unknown mosquito antigen that the parasite uses for entry
into the mosquito midgut, a critical step in
the Plasmodium parasite's development. The scientists
produced an antibody that acts as a blanket to
prevent the parasite from accessing the mosquito midgut
antigen. Their research showed that the
antibodies were effective against multiple malaria
parasites and could potentially provide the basis for
a future "universal" malaria transmissionÐblocking
vaccine.
Additional authors of the study are Aditi Alaganan,
Anil K. Ghosh, Akio Saito and Toin H. van
Kuppevelt.
The research was supported by the Ruth L. Kirschstein
Research Service Award in addition to
grants from the National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
The Malaria Research Institute at the Johns Hopkins
Bloomberg School of Public Health was
founded in 2001 to mount a broad program of basic science
research to treat and control malaria,
develop a vaccine and find new drug targets to prevent and
cure the deadly disease. Information about
the institute is available at
http://malaria.jhsph.edu.