Targeting Plasmodium ligands on mosquito salivary glands and midgut with aphage display peptide library

Despite vast efforts and expenditures in the past few decades, malaria cont inues to kill millions of persons every year, and new approaches for diseas e control are urgently needed. To complete its life cycle in the mosquito, Plasmodium, the causative agent of malaria, has to traverse the epithelia o f the midgut and salivary glands. Although strong circumstantial evidence i ndicates that parasite interactions with the two organs are specific, hardl y any information is available about the interacting molecules. By use of a phage display library, we identified a 12-aa peptide-salivary gland and mi dgut peptide 1 (SM1)-that binds to the distal lobes of the salivary gland a nd to the luminal side of the midgut epithelium, but not to the midgut surf ace facing the hemolymph or to ovaries. The coincidence of the tissues with which parasites and the SM1 peptide interact suggested that the parasite a nd peptide recognize the same surface ligand. In support of this hypothesis , the SM1 peptide strongly inhibited Plasmodium invasion of salivary gland and midgut epithelia. These experiments suggest a new strategy for the gene tic manipulation of mosquito vectorial capacity.