CRY Proteins: Stand-Alone Anthelmintics & Combination Therapy with NACHR Agonists
Animal Parasitic Diseases
2012 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 (Bt-Cry proteins) have been used commercially to kill soil nematodes that infect plants. The same Bt-Cry proteins and others isolated from different Bt strains or modified by mutagenesis, were demonstrated to kill parasitic Ascaris suum worms isolated from pigs in an in vitro culture system. Larvae isolated from the lung and intestines, along with adult worms from the intestines of pigs, were killed by Bt-Cry proteins in vitro comparable to other commercially available anti-parasitic drugs that were tested in parallel. A large amount of Bt-Cry protein has been produced and isolated to use in A. suum-infected pigs to validate its efficacy in vivo. These studies address a growing problem of anthelmintic drug resistance in livestock and can thus provide a novel alternative therapy to reduce parasite infection in food producing animals and in humans.