UC San Diego

To examine the anthelmintic properties of Bacillus thuringiensis (Bt) crystal proteins, this thesis investigates the therapeutic effects of Bt crystal protein 5B (Cry5B) as a single dose therapy against a roundworm infection in mice, and considers the synergistic potential of Cry5B in combination with a current anthelmintic. In order to examine the therapeutic effect of crude Cry5B spore crystal lysate (SCL), mice infected with Heligmosomoides bakeri L3 larvae were treated with a single dose of 50 mg/kg Cry5B SCL on day 15 post infection. The compound's effectiveness was determined by the reduction in fecal egg output and the final worm burden in treated versus placebo-treated control animals. This study finds Cry5B SCL to be highly efficacious in vivo. A follow-up experiment suggests that the crystals of Bt SCL are solely responsible for this therapeutic effect. This thesis further examines the therapeutic potential of Cry5B and levamisole against H. bakeri, using loss of motility as a marker of drug efficacy, and finds that the two compounds demonstrate strong synergy in vitro when combined at a 1:1 efficacious dose based upon their Fa30s. Further studies are warranted for an evaluation of any synergism between the two compounds in an in vivo system. Finally, the maintenance of Ancylostoma ceylanicum is detailed. This thesis confirms Cry5B's effectiveness as a therapeutic compound for the treatment of gastrointestinal nematode infections and establishes different systems in which to further test its efficacy and synergistic potential