CRY Proteins: Stand-Alone Anthelmintics & Combination Therapy with NACHR Agonists
Animal Parasitic Diseases
2013 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.
The work has demonstrated significant progress with two manuscripts accepted for publication in major parasitological journals. Firstly, it was demonstrated that Bt-Cry protein can inhibit the development of the most important intestinal nematode parasite of pigs and man (Ascaris species) when mixed with live worms cultured in an incubator with supporting media. This demonstrated a proof of principle with these bacteria-derived proteins not known before. Confirmation of the usefulness of these proteins as potential anti-parasitic treatment in livestock was then demonstrated by showing that pigs infected with Ascaris could be cleared of the intestinal infection with greater than 95% efficacy by orally feeding the Bt-Cry protein to the infected pigs (PLoS Negl Trop Dis. 2013 Jun 20;7(6):e2263. doi: 10.1371/journal.pntd.0002263. Print 2013 Jun). Secondly, the culture system used to show that Bt-Cry proteins killed Ascaris worms was developed into a more generalized test system against a variety of intestinal nematode parasites that infect man and livestock. This provides a convenient and low cost method for the development of new anti-parasitic drugs. This work has been accepted for publication in Plos One.