title: Inhibition of Plasmodium berghei Development in Mosquitoes by Effector Proteins Secreted from Asaia sp. Bacteria Using a Novel Native Secretion Signal.
abstract: Novel interventions are needed to prevent the transmission of the Plasmodium parasites that cause malaria. One possible method is to supply mosquitoes with antiplasmodial effector proteins from bacteria by paratransgenesis. Mosquitoes have a diverse complement of midgut microbiota including the Gram-negative bacteria Asaia bogorensis. This study presents the first use of Asaia sp. bacteria for paratransgenesis against P. berghei. We identified putative secreted proteins from A. bogorensis by a genetic screen using alkaline phosphatase gene fusions. Two were secreted efficiently: a siderophore receptor protein and a YVTN beta-propeller repeat protein. The siderophore receptor gene was fused with antiplasmodial effector genes including the scorpine antimicrobial peptide and an anti-Pbs21 scFv-Shiva1 immunotoxin. Asaia SF2.1 secreting these fusion proteins were fed to mosquitoes and challenged with Plasmodium berghei-infected blood. With each of these effector constructs, significant inhibition of parasite development was observed. These results provide a novel and promising intervention against malaria transmission.
authors.affiliation: Department of Biological Sciences, Duquesne University, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Bongio
authors.affiliation: Department of Biological Sciences, Duquesne University, Pittsburgh, Pennsylvania, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lampe
mesh_terms: D016947:Acetobacteraceae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004064:Digestive System; D018014:Gene Transfer Techniques; D008288:Malaria / Q000517:prevention & control*; D008969:Molecular Sequence Data; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development; D021382:Protein Sorting Signals; D011956:Receptors, Cell Surface / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D021382:Protein Sorting Signals; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C035902:siderophore receptors