Researchers find essential proteins for critical stage of malaria

January 16, 2009

Researchers at the Johns Hopkins Malaria Research Institute (JHMRI) have identified the molecular components that enable the malaria-causing parasite Plasmodium to infect the salivary glands of the Anopheles mosquito-a critical 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 (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 January 16 in the open-access journal PLoS Pathogens.

Malaria is estimated to infect 300 to 500 million people worldwide resulting in over 1 million deaths each year. JHMRI was established in 2001 at the Bloomberg School of Public Health to mount a broad program of basic-science research to treat and control the deadly disease.

Through a series of experiments, Marcelo Jacobs-Lorena, PhD, and his colleagues 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," explained Jacobs-Lorena. "We are learning more and more about how the malaria parasite develops inside the mosquito, which could lead to novel approaches for disrupting its lifecycle and preventing the spread of malaria."

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