Researchers Find Essential Proteins for Final Stage of Malaria Transmission Cycle

Researchers at the Johns Hopkins Malaria Research Institute (JHMRI) 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 (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 January 16 edition of PLoS Pathogens.

Through a series of experiments, 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,” explained Marcelo Jacobs-Lorena, PhD, an author of the study and professor with the Johns Hopkins Bloomberg School of Public Health’s W. Harry Feinstone Department of Molecular Microbiology and Immunology.

“Identification of molecular recognition mechanisms between the parasite and mosquito vector provides novel targets for further investigation aimed at interrupting malaria transmission,” said co-author Nirbhay Kumar, PhD, also a professor in the Bloomberg School's W. Harry Feinstone Department of Molecular Microbiology and Immunology. 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 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.

Additional authors of “Malaria Parasite Invasion of the Mosquito Salivary Gland Requires Interaction Between the Plasmodium TRAP and the Anopheles Saglin Proteins” 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.