title: Interrupting malaria transmission by genetic manipulation of anopheline mosquitoes.
abstract: Malaria ranks among the deadliest infectious diseases that kills more than one million persons every year. The mosquito is an obligatory vector for malaria transmission. In the mosquito, Plasmodium undergoes a complex series of developmental events that includes transformation into several distinct morphological forms and the crossing of two different epithelia--midgut and salivary gland. Circumstantial evidence suggests that crossing of the epithelia requires specific interactions between Plasmodium and epithelial surface molecules. By use of a phage display library we have identified a small peptide-SM1--that binds to the surfaces of the mosquito midgut and salivary glands. Transgenic Anopheles stephensi mosquitoes expressing a SM1 tetramer from a blood-inducible and gut-specific promoter are substantially impaired in their ability to sustain parasite development and transmission. A second effector gene, phospholipase A2, also impairs parasite transmission in transgenic mosquitoes. These findings have important implications for the development of new strategies for malaria control.
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA. mlorena@jhsph.edu
authors.forename: Marcelo
authors.initials: M
authors.lastname: Jacobs-Lorena
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics* / Q000469:parasitology*; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D007303:Insect Vectors / Q000235:genetics* / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology / Q000635:transmission*; D030781:Organisms, Genetically Modified / Q000235:genetics / Q000469:parasitology; D019151:Peptide Library; D010961:Plasmodium / Q000254:growth & development*; D014170:Transformation, Genetic
chemical_list: D019476:Insect Proteins; D019151:Peptide Library