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: Weiguo Fang, Joel Vega-Rodríguez, Anil K Ghosh, Marcelo Jacobs-Lorena, Angray Kang, Raymond J St Leger
• Journal: Science (New York, N.Y.) (Science) Vol. 331 Issue 6020 Pg. 1074-7 (Feb 25 2011) ISSN: 1095-9203 [Electronic] United States
• PMID: 21350178 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Protozoan
• Defensins
• Oligopeptides
• Protozoan Proteins
• SM1 peptide
• circumsporozoite protein, Protozoan
• scorpine

Topics

• Animals
• Anopheles (microbiology, parasitology, physiology)
• Antibodies, Protozoan (immunology)
• Base Sequence
• Cloning, Molecular
• Defensins (genetics, metabolism)
• Feeding Behavior
• Female
• Hemolymph (metabolism, microbiology, parasitology)
• Humans
• Insect Vectors (microbiology, parasitology, physiology)
• Malaria, Falciparum (transmission)
• Metarhizium (genetics, physiology)
• Molecular Sequence Data
• Oligopeptides (genetics, metabolism)
• Organisms, Genetically Modified
• Pest Control, Biological
• Plasmodium falciparum (physiology)
• Protozoan Proteins (immunology)
• Salivary Glands (metabolism, parasitology)
• Spores, Fungal (physiology)
• Sporozoites (physiology)
• Transformation, Genetic
• Transgenes