A Broad-Based Mosquito Yeast Interfering RNA Pesticide Targeting Rbfox1 Represses Notch Signaling and Kills Both Larvae and Adult Mosquitoes.

Keshava Mysore,Max P Scheel,Longhua Sun,Molly Duman-Scheel,David W Severson,Jessica Igiede,Limb K Hapairai,Na Wei,Ping Li,Joseph B Roethele,Nicholas D Scheel,Chien-Wei Wang

doi:10.3390/pathogens10101251

Keshava Mysore, Max P Scheel + Show 10 more

Open Access

https://doi.org/10.3390/pathogens10101251

Copy DOI

Abstract

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.

Highlights

Vector control is the primary mechanism for mosquito-borne disease prevention, resistance to all classes of chemical insecticides has been documented worldwide in a variety of disease vector mosquitoes [1]
Rbfox1.457 small interfering RNA (siRNA) corresponds to a target sequence in Rbfox1 that is conserved in multiple species of disease vector mosquitoes (Table S1) [26]
The results of this study suggest that Rbfox1.457 yeast, a dual-action adulticidal and larvicidal interfering RNA pesticides (IRPs) with a target site conserved in the Rbfox1 gene of many species of mosquitoes (Table S1), could potentially be used as a new means of controlling Aedes, Anopheles, and Culex mosquitoes at multiple stages of the mosquito life cycle (Figures 1, 2 and 4)

Summary

Introduction

Vector control is the primary mechanism for mosquito-borne disease prevention, resistance to all classes of chemical insecticides has been documented worldwide in a variety of disease vector mosquitoes [1]. The potential for unintended deleterious impacts of insecticides on non-target target organisms, including humans, is of concern and is continuously monitored [2] Given these issues, the successful prevention of arthropodborne infectious diseases will require new classes of environmentally safe insecticides and novel mosquito control technologies [3]. It was hypothesized that these interfering RNA pesticides (IRPs) will kill multiple types of mosquitoes during the larval and adult stages, yet pose little or no threat to non-target organisms To further evaluate this hypothesis, the present investigation pursued characterization of a putative adulticidal and larvicidal IRP with a conserved target site in mosquito Rbfox genes

Methods

Results

Conclusion