title: Development of transgenic fungi that kill human malaria parasites in mosquitoes.
abstract: Metarhizium anisopliae infects mosquitoes through the cuticle and proliferates in the hemolymph. To allow M. anisopliae to combat malaria in mosquitoes with advanced malaria infections, we produced recombinant strains expressing molecules that target sporozoites as they travel through the hemolymph to the salivary glands. Eleven days after a Plasmodium-infected blood meal, mosquitoes were treated with M. anisopliae expressing salivary gland and midgut peptide 1 (SM1), which blocks attachment of sporozoites to salivary glands; a single-chain antibody that agglutinates sporozoites; or scorpine, which is an antimicrobial toxin. These reduced sporozoite counts by 71%, 85%, and 90%, respectively. M. anisopliae expressing scorpine and an [SM1](8):scorpine fusion protein reduced sporozoite counts by 98%, suggesting that Metarhizium-mediated inhibition of Plasmodium development could be a powerful weapon for combating malaria.
authors.affiliation: Department of Entomology, University of Maryland, 4112 Plant Sciences Building, College Park, MD 20742, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Fang
authors.forename: Joel
authors.initials: J
authors.lastname: Vega-Rodríguez
authors.forename: Anil K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Marcelo
authors.initials: M
authors.lastname: Jacobs-Lorena
authors.forename: Angray
authors.initials: A
authors.lastname: Kang
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: St Leger
mesh_terms: D000818:Animals; D000852:Anopheles / Q000382:microbiology* / Q000469:parasitology* / Q000502:physiology; D000913:Antibodies, Protozoan / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D023082:Defensins / Q000235:genetics / Q000378:metabolism; D005247:Feeding Behavior; D005260:Female; D006458:Hemolymph / Q000378:metabolism / Q000382:microbiology / Q000469:parasitology; D006801:Humans; D007303:Insect Vectors / Q000382:microbiology* / Q000469:parasitology* / Q000502:physiology; D016778:Malaria, Falciparum / Q000635:transmission; D052981:Metarhizium / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D030781:Organisms, Genetically Modified; D010572:Pest Control, Biological; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000276:immunology; D012469:Salivary Glands / Q000378:metabolism / Q000469:parasitology; D013172:Spores, Fungal / Q000502:physiology; D034101:Sporozoites / Q000502:physiology; D014170:Transformation, Genetic; D019076:Transgenes
chemical_list: D000913:Antibodies, Protozoan; D023082:Defensins; D009842:Oligopeptides; D015800:Protozoan Proteins; C535223:SM1 peptide; C041595:circumsporozoite protein, Protozoan; C407873:scorpine