The mosquito's innate immune system controls both and bacterial infections. We investigated the competitiveness of mosquitoes genetically modified to alter expression of their own anti- immune genes in a mixed-cage population with wild-type mosquitoes. We observed that genetically modified mosquitoes with increased immune activity in the midgut tissue did not have an observed fitness disadvantage and showed reduced microbial loads in both the midgut and reproductive organs. These changes result in a mating preference of genetically modified males for wild-type females, whereas wild-type males prefer genetically modified females. These changes foster the spread of the genetic modification in a mosquito cage population.
The mosquito’s innate immune system defends against a variety of pathogens, and the conserved siRNA pathway plays a central role in the control of viral infections. Here, we show that transgenic overexpression of Dicer2 (Dcr2) or R2d2 resulted in an accumulation of 21-nucleotide viral sequences that was accompanied by a significant suppression of dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) replication, thus indicating the broad-spectrum antiviral response mediated by the siRNA pathway that can be applied for the development of novel arbovirus control strategies. Interestingly, overexpression of Dcr2 or R2d2 regulated the mRNA abundance of a variety of antimicrobial immune genes, pointing to additional functions of DCR2 and R2D2 as well as cross-talk between the siRNA pathway and other immune pathways. Accordingly, transgenic overexpression of Dcr2 or R2d2 resulted in a lesser proliferation of the midgut microbiota and increased resistance to bacterial and fungal infections.
Given the continued high prevalence of mosquito-transmitted diseases, there is a clear need to develop novel disease and vector control strategies. Biopesticides of microbial origin represent a promising source of new approaches to target disease-transmitting mosquito populations. Here, we describe the development and characterization of a novel mosquito biopesticide, derived from an air-dried, nonlive preparation of the bacterium Chromobacterium sp. Panama (family: Neisseriaceae). This preparation rapidly and effectively kills the larvae of prominent mosquito vectors, including the dengue and Zika vector Aedes aegypti and the human malaria vector Anopheles gambiae. During semi-field trials in Puerto Rico, we observed high efficacy of the biopesticide against field-derived A. aegypti populations, and against A. aegypti and Culex species larvae in natural breeding water, indicating the suitability of the biopesticide for use under more natural conditions. In addition to high efficacy, the nonlive Csp_P biopesticide has a low effective dose, a long shelf life, and high heat stability and can be incorporated into attractive larval baits, all of which are desirable characteristics for a biopesticide.
IMPORTANCE We have developed a novel preparation to kill mosquitoes from an abundant soil bacterium, Chromobacterium sp. Panama. This preparation is an air-dried powder containing no live bacteria, and it can be incorporated into an attractive bait and fed directly to mosquito larvae. We demonstrate that the preparation has broad spectrum activity against the larval form of the mosquitoes responsible for the transmission of malaria and the dengue, chikungunya, yellow fever, West Nile, and Zika viruses, as well as mosquito larvae that are already resistant to commonly used mosquitocidal chemicals. Our preparation possesses many favorable traits: it kills at a low dosage, and it does not lose activity when exposed to high temperatures, all of which suggest that this preparation could eventually become an effective new tool for controlling mosquitoes and the diseases they spread.
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