CRY Proteins: Stand-Alone Anthelmintics & Combination Therapy with NACHR Agonists
Animal Parasitic Diseases
2011 Annual Report
1a.Objectives (from AD-416)
Identify functional genetic variations that modulate the immune responses by swine to mucosal pathogens. In-house research has demonstrated that parasitic infection and clearance of the parasite with anthelmintics can modulate vaccine efficacy against mucosal pathogens. On the basis of these results, the application of novel anthelmintics could eliminate infections that negatively affect the health and vaccine efficacy of swine. Validation of this hypothesis will improve vaccination efficiency against mucosal pathogens.
1b.Approach (from AD-416)
ARS will evaluate oral treatment of rats and pigs with Bt-Cry proteins to evaluate the clearance of the gastrointestinal nematode parasites N. brasiliensis and A. suum, respectively, and determine local changes in mucosal immune function. This information will be used by both ARS and the Cooperator to jointly develop studies that focus on improved parasite control and enhanced immune function. The Cooperator is interested in evaluating the efficacy of Bacillus thuringiensis (Bt) Cry proteins in clearing infections of the mucosal parasites Nippostrongylus brasiliensis and Ascaris suum. Nippostrongylus brasiliensis is model parasite similar to the economically important trichostrongyle parasites of cattle, sheep and goats, and Ascaris suum is the most prevalent nematode parasite of swine causing liver condemnation, reduced feed efficiency, and interference with immune function. This will allow a broader application of this product for use in helminthes that infect livestock and man and will be used as data for a funded four year grant proposal submitted to NIH.
Bacillus thuringiensis crystal proteins were demonstrated to kill Ascaris suum larvae in an in vitro culture system. Crystal protein isolated from the soil bacteria B. thuringiensis have been used commercially to kill soil nematodes that infect plants. The same group of proteins was tested against larval stages of A. suum, the pig parasitic nematode. Both the late third stage larvae from the lung and early and mid-fourth stage from the intestines were killed by the crystal protein in vitro comparable to other commercially available anthelmintics that were tested in parallel. The impact of this observation relates to the growing problem of anthelmintic resistance in livestock and can thus provide a novel alternative therapy using a product that is already present in the human food chain.