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Malaria Parasite Invasion of the Mosquito Salivary Gland Requires Interaction between the Plasmodium TRAP and the Anopheles Saglin Proteins

WWARN Published Date

from PLoS Pathogens:

Transmission of Plasmodium, the causative agent of malaria, requires the completion of a complex life cycle in the mosquito, which includes invasion of the salivary glands. This invasion depends on the recognition of mosquito salivary gland surface components by the parasite. This work demonstrates that interaction between the salivary-gland-specific surface protein saglin and the parasite surface protein TRAP is essential for invasion to occur. A better understanding of the mechanisms used by the parasite to develop in the mosquito may lead to novel approaches to intervene with the spread of the disease.

SM1 is a twelve-amino-acid peptide that binds tightly to the Anopheles salivary gland and inhibits its invasion by Plasmodium sporozoites. By use of UV-crosslinking experiments between the peptide and its salivary gland target protein, we have identified the Anopheles salivary protein, saglin, as the receptor for SM1. Furthermore, by use of an anti-SM1 antibody, we have determined that the peptide is a mimotope of the Plasmodium sporozoite Thrombospondin Related Anonymous Protein (TRAP). TRAP binds to saglin with high specificity. Point mutations in TRAP's binding domain A abrogate binding, and binding is competed for by the SM1 peptide. Importantly, in vivo down-regulation of saglin expression results in strong inhibition of salivary gland invasion. Together, the results suggest that saglin/TRAP interaction is crucial for salivary gland invasion by Plasmodium sporozoites.

https://journals.plos.org/plospathogens/article/comments?id=10.1371/journal.ppat.1000265