A Broad-Based Mosquito Yeast Interfering RNA Pesticide Targeting <i>Rbfox1</i> Represses <i>Notch</i> Signaling and Kills Both Larvae and Adult Mosquitoes
Keshava Mysore,
Longhua Sun,
Limb K. Hapairai,
Chien-Wei Wang,
Joseph B. Roethele,
Jessica Igiede,
Max P. Scheel,
Nicholas D. Scheel,
Ping Li,
Na Wei,
David W. Severson,
Molly Duman-Scheel
Affiliations
Keshava Mysore
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Raclin-Carmichael Hall, 1234 Notre Dame Ave., South Bend, IN 46617, USA
Longhua Sun
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Raclin-Carmichael Hall, 1234 Notre Dame Ave., South Bend, IN 46617, USA
Limb K. Hapairai
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Raclin-Carmichael Hall, 1234 Notre Dame Ave., South Bend, IN 46617, USA
Chien-Wei Wang
Eck Institute for Global Health, The University of Notre Dame, South Bend, IN 46556, USA
Joseph B. Roethele
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Raclin-Carmichael Hall, 1234 Notre Dame Ave., South Bend, IN 46617, USA
Jessica Igiede
Eck Institute for Global Health, The University of Notre Dame, South Bend, IN 46556, USA
Max P. Scheel
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Raclin-Carmichael Hall, 1234 Notre Dame Ave., South Bend, IN 46617, USA
Nicholas D. Scheel
Eck Institute for Global Health, The University of Notre Dame, South Bend, IN 46556, USA
Ping Li
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Raclin-Carmichael Hall, 1234 Notre Dame Ave., South Bend, IN 46617, USA
Na Wei
Eck Institute for Global Health, The University of Notre Dame, South Bend, IN 46556, USA
David W. Severson
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Raclin-Carmichael Hall, 1234 Notre Dame Ave., South Bend, IN 46617, USA
Molly Duman-Scheel
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Raclin-Carmichael Hall, 1234 Notre Dame Ave., South Bend, IN 46617, USA
Prevention of mosquito-borne infectious diseases will require new classes of environmentally safe insecticides and novel mosquito control technologies. Saccharomyces cerevisiae was engineered to express short hairpin RNA (shRNA) corresponding to mosquito Rbfox1 genes. The yeast induced target gene silencing, resulting in larval death that was observed in both laboratory and outdoor semi-field trials conducted on Aedes aegypti. High levels of mortality were also observed during simulated field trials in which adult females consumed yeast delivered through a sugar bait. Mortality correlated with defects in the mosquito brain, in which a role for Rbfox1 as a positive regulator of Notch signaling was identified. The larvicidal and adulticidal activities of the yeast were subsequently confirmed in trials conducted on Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus, yet the yeast had no impact on survival of select non-target arthropods. These studies indicate that yeast RNAi pesticides targeting Rbfox1 could be further developed as broad-based mosquito larvicides and adulticides for deployment in integrated biorational mosquito control programs. These findings also suggest that the species-specificity of attractive targeted sugar baits, a new paradigm for vector control, could potentially be enhanced through RNAi technology, and specifically through the use of yeast-based interfering RNA pesticides.
