The search for novel insecticide targets in the post-genomics era, with a specific focus on G-protein coupled receptors

Abstract

Insects are considered pests globally, implicated in the destruction of agricultural fields and transmission of pathogens that cause deadly human diseases, such as dengue, Zika and malaria. The diversity of the insecticide arsenal has remained stagnant for decades, but the recent rise of insecticide resistance fueled the discovery of novel modes of action, and the power of genomics has reinvigorated this search. This review discusses the importance of comparative and functional insect genomics in the identification of potential gene targets for an insecticidal mode of action with low off-target toxicity. Due to the global participation in the sequencing and annotation of insect genomes, the targeting of specific genes with molecular tools like RNAi and CRISPR/Cas9 for genome engineering and consequent functional identification and validation has become more efficient. While there are multiple avenues to explore for insecticidal candidates, this review identifies G-protein coupled receptors as attractive targets, and hones in on the octopamine and dopamine receptors due to their potential.

Progress and Prospects of CRISPR/Cas Systems in Insects and Other Arthropods

“…Moreover, the CRISPR/Cas9 system has also been used to verify functional genes associated with insect physiological processes, such as embryonic development and abdominal segment determination (Bi et al, 2016 ; Huang et al, 2016 ; Li X. Y. et al, 2016 ; Liu H. et al, 2017 ), female sex pheromone perception (Zhu et al, 2016 ), sex determination and life span (Xu et al, 2017 ; Zhang Z. et al, 2017 ), pigmentation pattern formation (Khan et al, 2017 ), eyespot formation and development in butterflies (Perry et al, 2016 ; Zhang and Reed, 2016 ), and migration behavior (Markert et al, 2016 ). Meanwhile, insect resistance has also been analyzed using CRISPR/Cas9 genome manipulation tools (Douris et al, 2016 ; Wang J. et al, 2016 ; Zimmer et al, 2016 ; Bajda et al, 2017 ; Ngai and McDowell, 2017 ). Furthermore, the aim of some of the reviewed studies was to validate CRISPR systems by knocking out genes that have a visible mutant phenotype (Wang et al, 2013 ; Liu Y. et al, 2014 ; Abudayyeh et al, 2016 ; Kim H. et al, 2017 ).…”

The Insecticidal Activity of Rhinella schneideri (Werner, 1894) Paratoid Secretion in Nauphoeta cinerea Cocroaches

“…Nowadays, pesticide resistance has become a serious problem, with an estimated 489 species of insects resistant to the most widely used synthetic pesticides, such as pyrethroids, organophosphates and chlorinated hydrocarbons [ 1 , 2 , 3 ]. With the increased resistance in pest insects in focus, there is an urgency for identifying novel insecticidal molecules with alternative modes of action, preferable of natural origins [ 2 ].…”

The role of G protein‐coupled receptor‐related genes in cytochrome P450‐mediated resistance of the house fly, Musca domestica (Diptera: Muscidae), to imidacloprid

“…They comprise a large family of membrane‐bound receptors that mediate many critical biological processes in vertebrates and invertebrates (Hill et al ., ) by recognizing extracellular ligands. The processes in which they are involved include developmental, visual, gustatory, olfactory sensing, homeostasis and hormonal regulation (Audsley and Down, ; Ngai and McDowell, ). GPCRs are therefore attractive targets for drug discovery in the pharmaceutical industry, with approximately 50% of human medications exerting their effects via this protein family (Filmore, ).…”