Trypsin-modulating oostatic factor: a potential new larvicide for mosquito control

Abstract

Trypsin-modulating oostatic factor (TMOF), a mosquito decapeptide, terminates trypsin biosynthesis in the mosquito gut. The hormone is secreted from the ovary, starting 18·h after the blood meal, circulates in the hemolymph, binds to a gut receptor and stops trypsin biosynthesis by exerting a translational control on trypsin mRNA. Because of the unique primary amino acid sequence of the hormone (YDPAPPPPPP) and its stable three-dimensional conformation, TMOF is not degraded by gut proteolytic enzymes and can traverse the gut epithelial cells into the hemolymph of adults and larvae. Using this unique property, hormone fed to different species of mosquito larvae stops food digestion and causes larval mortality. To determine the shortest amino acid sequence that can bind to the gut receptor and still cause high larval mortality, 25 analogues of TMOF were synthesized and tested. The tetrapeptide (YDPA) was as effective as the decapeptide, indicating that the binding to the gut receptor is at the N-terminus of the molecule. Cloning and expressing the hormone on the coat protein of tobacco mosaic virus (TMV) in Chlorella sp. and Saccharomyces cerevisiae cells and feeding the recombinant cells to mosquito larvae caused larval mortality. These results indicate that TMOF can be used as a new biorational insecticide against mosquito larvae.

A viral chitinase enhances oral activity of TMOF

“…In a recent study on Spodoptera littoralis larvae, the presence of Aea-TMOF receptors on the basolateral membrane of midgut cells has been hypothesized (Lemeire et al, 2008). The effect of ingested and injected Aea-TMOF on trypsin biosynthesis (Nauen et al, 2001) and on the growth of H. virescens larvae (Tortiglione et al, 2002;2003) also suggests the presence of a TMOF-like hormone in Lepidoptera, and, therefore, of receptors similar to those identified in mosquitoes. In the present study we show that FITC-TMOF crosses H. virescens larval midgut by diffusion through the paracellular pathway ( Fig.…”

“…virescens larvae (Nauen et al, 2001), even when expressed in transgenic plants (Tortiglione et al, 2002;2003). The strategy pursued in these latter studies was to deliver in the gut, with different constructs, a TMOF precursor made of multiple peptide units, spaced by dibasic residues, Arg-Arg, as potential post-translational cleavage site.…”

“…This apparent contrast can be reasonably reconciled by taking into consideration the specific biological features of this peptide. According to the model described in their review by Borovsky et al (2003), TMOF produced from…”

“…These results stimulated the idea of using ChiA in combination with Aea-TMOF, which targets receptors expressed in the basolateral membrane of epithelial midgut cells and causes the inhibition of trypsin synthesis, thus impairing the insect digestive processes (Borovsky et al, 1994;Nauen et al, 2001;Borovsky and Meola, 2004). Aea-TMOF exerts mild insecticide activity on Heliothis virescens larvae when expressed in transgenic tobacco plants (Tortiglione et al, 2002;2003), and negatively interferes with larval growth of the tobacco budworm (Heliothis virescens), when fused to Tobacco…”

Residual effects of TMOF–Bti formulations against 1st instar Aedes aegypti Linnaeus larvae outside laboratory

“…The hormone is secreted from the ovary, starting 18 hours after the blood meal, circulates in the hemolymph, binds to a gut receptor and stops trypsin biosynthesis by exerting a translational control on trypsin mRNA [9] . TMOF binds a gut receptor and induces phosphorylation of a gut protein, which is cleaved by a protease and released from the gut [10] .…”