Barcoded Asaia bacteria enable mosquito in vivo screens and identify novel systemic insecticides and inhibitors of malaria transmission.

Angelika Sturm,Avinash Sheshachalam,Kirandeep Samby,Martijn W Vos,Guido Favia,Koen J Dechering,Karin M J Koolen,Rob Henderson,Maarten Eldering,Esperanza Herreros,Luis Teixeira

doi:10.1371/journal.pbio.3001426

Abstract

This work addresses the need for new chemical matter in product development for control of pest insects and vector-borne diseases. We present a barcoding strategy that enables phenotypic screens of blood-feeding insects against small molecules in microtiter plate-based arrays and apply this to discovery of novel systemic insecticides and compounds that block malaria parasite development in the mosquito vector. Encoding of the blood meals was achieved through recombinant DNA-tagged Asaia bacteria that successfully colonised Aedes and Anopheles mosquitoes. An arrayed screen of a collection of pesticides showed that chemical classes of avermectins, phenylpyrazoles, and neonicotinoids were enriched for compounds with systemic adulticide activity against Anopheles. Using a luminescent Plasmodium falciparum reporter strain, barcoded screens identified 48 drug-like transmission-blocking compounds from a 400-compound antimicrobial library. The approach significantly increases the throughput in phenotypic screening campaigns using adult insects and identifies novel candidate small molecules for disease control.

Highlights

Parasites and viruses that are carried by mosquitoes cause diseases such as malaria, dengue, or yellow fever
We envisaged to use DNA-encoded blood meals in 96-well plates presented to hematophagous insects, allowing deconvolution of the feeding pattern
We explored suitability of this screening principle for phenotypic screening for systemic insecticides using fipronil as a reference compound

Summary

Introduction

Parasites and viruses that are carried by mosquitoes cause diseases such as malaria, dengue, or yellow fever. The use of insecticides has had large impact on control of malaria [1]. Since World War II, the range of chemical scaffolds with insecticide activity has slowly expanded, resulting in 55 chemically distinct classes of marketed insecticides available in 2019 [2]. Resistance to these molecules has developed at a similar rate as a result of widespread use in crop protection, community and household spraying, and impregnation of bed nets [3]. As a more targeted approach, the use of oral insecticides in drug-based vector

Methods

Results

Conclusion