Exploiting host molecules to augment mycoinsecticide virulence


35 that participates in critical host physiological processes, thereby minimizing nontarget effects. Insect diuretic hormones participate in the regulation of water balance, and MSDH belongs to the corticotropin-releasing factor– related family of peptides. Synthetic MSDH has been shown to stimulate fluid excretion in vivo, resulting in pronounced loss of fluid through the gut and the epidermis, decreased feeding and ultimately insect death8–10. TMOFs are unblocked decaand hexa-peptides that terminate trypsin biosynthesis in the insect gut and are found in the ovaries of insects that include both mosquitoes and flies. Aea-TMOF circulates in the hemolymph, binds to gut receptors on the hemolymph side of the gut and inhibits trypsin biosynthesis by exerting a translational control on trypsin mRNA11. Because TMOF resists proteolysis in the gut and easily traverses the gut epithelial cells into the hemolymph in adults and larvae, it was fed to different species of mosquito larvae in which it caused inhibition of food digestion and anorexia, ultimately leading to starvation and death12. TMOF is currently under development as an insecticide and appears to be very specific against mosquitoes with minimal nontarget effects13. Indeed, TMOFs from different insects have different peptide sequences (e.g., the AeaTMOF sequence is YDPAPPPPPP, whereas the gray flesh fly, Sarcophaga bullata, SbTMOF sequence is NPTNLH14). MSDH-Gly (42 amino acids) and the A. aegypti Aea-TMOF peptides were expressed in B. bassiana by transformation of expression vectors containing a constitutive B. bassiana-derived gpd promoter and the nucleotide sequence corresponding to the insecticides has resulted in substantial damage to ecosystems and the emergence of insecticide-resistant agricultural pests. Mosquitoes are vectors of many human and animal infectious diseases that cause death and economic hardship. World Health Organization (WHO; Geneva) recommendations suggest the use of different control strategies as part of integrated vector management control to prevent the emergence of insecticide-resistant mosquitoes. Effective strategies, however, for long-term reduction of mosquito populations remain elusive2. Entomopathogenic fungi are virulent to a wide range of Lepidoptera as well as mosquitoes and have been considered as possible candidates for reducing disease transmission of vectorborne infectious agents3,4. Methods have been developed for delivery of these agents in agricultural settings as well as to adult and larval mosquitoes, and the fungi appear to be equally (or more) effective against insecticide-resistant strains as compared with their insecticide-susceptible parental strains5–7. To test whether host molecules can be used to increase the virulence of entomopathogenic fungi, we engineered two insect peptides—Manduca sexta diuretic hormone (MSDH) and A. aegypti trypsinmodulating oostatic factor (Aea-TMOF)—in B. bassiana, which expresses and secretes these hormones as it infects its host. Our idea was that the exogenously produced host peptide hormone would disrupt the normal endocrine or neurological balance of the host, making it more susceptible to the invading fungus. As candidates, we chose a potential broad host range target (MSDH) as well as a more host-specific peptide (TMOF) target Exploiting host molecules to augment mycoinsecticide virulence

DOI: 10.1038/nbt.2080

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@article{Fan2012ExploitingHM, title={Exploiting host molecules to augment mycoinsecticide virulence}, author={Yanhua Fan and Dov Borovsky and Chloe Hawkings and Almudena Ortiz-Urquiza and Nemat O. Keyhani}, journal={Nature Biotechnology}, year={2012}, volume={30}, pages={35-37} }