Abstract
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.
Highlights
Plasmodium spp., the causative agent of malaria, is responsible for about 500 million clinical cases and about 2 million deaths every year, mostly of African children [1]
We found that the antibody strongly inhibited P. falciparum sporozoite salivary gland invasion (Figure 6A), suggesting that saglin plays a central role in this process
We report that the salivary gland protein saglin is a receptor and that the sporozoite protein Thrombospondin Related Anonymous Protein (TRAP) is a ligand in this invasion
Summary
Plasmodium spp., the causative agent of malaria, is responsible for about 500 million clinical cases and about 2 million deaths every year, mostly of African children [1]. Unlike the other two major infectious disease killers-AIDS and tuberculosis-malaria depends on an intermediate insect vector for transmission to occur. Plasmodium transmission is initiated with the ingestion by the female mosquito, of gametocytes from an infected individual. Gametocytes differentiate into male and female gametes that mate to produce zygotes within the mosquito midgut. These differentiate into motile ookinetes that invade the midgut epithelium. After emerging on the hemocoel side, ookinetes differentiate into sessile oocysts that mature one or two weeks later (depending on Plasmodium species) releasing thousands of sporozoites into the open hemolymph circulation. The transmission cycle is completed when an infected mosquito bites another individual releasing some of its sporozoites
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