Journal Article

Development of Transgenic Fungi That Kill Human Malaria Parasites in Mosquitoes

Ghosh, Anil K, Jacobs-Lorena, Marcelo, St. Leger, Raymond J, Vega-Rodríguez, Joel, Kang, Angray, Fang, Weiguo

2011

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animals / Anopheles - microbiology / Anopheles - parasitology / Anopheles - physiology / antibodies / Antibodies, Protozoan - immunology / Antimicrobial agents / Aquatic insects / Base Sequence / Biological and medical sciences / Biological control / blood meal / Cloning, Molecular / Counting / Culicidae / Defensins - genetics / Defensins - metabolism / Disease control / Feeding Behavior / Female / Fundamental and applied biological sciences. Psychology / Fungal spores / Fungi / genetically modified organisms / hemolymph / Hemolymph - metabolism / Hemolymph - microbiology / Hemolymph - parasitology / Humans / Infections / Inhibition / Insect vectors / Insect Vectors - microbiology / Insect Vectors - parasitology / Insect Vectors - physiology / Malaria / Malaria, Falciparum - transmission / Medically important nuisances and vectors, pests of stored products and materials: population survey and control / Metarhizium / Metarhizium - genetics / Metarhizium - physiology / Metarhizium anisopliae / midgut / Molecular Sequence Data / Mosquitoes / Mosquitos / Oligopeptides - genetics / Oligopeptides - metabolism / Organisms, Genetically Modified / Parasites / Peptides / Pest Control, Biological / Plasmodium / Plasmodium falciparum - physiology / Proteins / Protozoan Proteins - immunology / Recombinant / Salivary glands / Salivary Glands - metabolism / Salivary Glands - parasitology / Spores, Fungal - physiology / Sporozoites / Sporozoites - physiology / Toxins / Transformation, Genetic / Transgenes / Transgenic insects / travel / Vector-borne diseases / Vectors. Intermediate hosts