Engineered Probiotics For Farm Animal and Human Nematodes

The goal of this proposed research is to develop and optimize a revolutionary engineered food grade/probiotic anthelmintic for treating gastrointestinal (GI) tract nematodes of farm animals and humans that would be well along the path towards commercialization.Objectives:1. Cry5B optimization studies: (a) Optimize Cry5B sequence to optimally and specifically target the parasites of interest in this grant, namely cyathostomin parasites of horses (monogastric farm animal) and H. contortus parasites of sheep/goats (small ruminant farm animals). (b) Study the spectrum of action of Cry5B against other GI nematodes important for veterinary medicine.2. Building a commercially-viable food grade/probiotic Cry5B anthelmintic strain: (a) Optimize expression of Cry5B in selected Bacillus strain using unique expression strategies. (b) Optimize biomass production of this uniquely engineered Bacillus strain in fermenters.3. Formulation studies and in vivo testing in large animals: (a) Formulate food
grade/probiotic Cry5B strain to protect Cry5B from premature digestion (stomach of horses; rumen, reticulum, omasumof ruminants) and release Cry5B at parasites (intestine of horses; abomasum of ruminants). (b) Test unformulated and formulated Cry5B in vivo (horses infected with cyathostomins, P. equorum; lambs/goats infected with H. contortus and other strongyles).