How do oral insecticidal compounds cross the insect midgut epithelium?

The use of oral insecticidal molecules (small molecules, peptides, dsRNA) via spray or plant mediated applications represents an efficient way to manage damaging insect species. With the exception of Bt toxins that target the midgut epithelium itself, most of these compounds have targets that lie within the hemocoel (body) of the insect. Because of this, one of the greatest factors in determining the effectiveness of an oral insecticidal compound is its ability to traverse the gut epithelium and enter the hemolymph. However, for many types of insecticidal compounds, neither the pathway taken across the gut nor the specific genes which influence uptake are fully characterized. Here, we review how different types of insecticidal compounds enter or cross the midgut epithelium through passive (diffusion) or active (transporter based, endocytosis) routes. A deeper understanding of how insecticidal molecules cross the gut will help to best utilize current insecticides and also provide for more rational design of future ones. [Display omitted] •The ability of insecticidal molecules to cross the insect midgut is vital to their ability to kill insects.•Transporter proteins likely play a role in the penetration of small molecules across the gut but remain understudied.•A number of studies have identified the molecular components of protein uptake including receptors on the apical membrane.•Much still remains unclear about the fate of dsRNA once it is taken up into midgut cells.