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**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** GASTROINTESTINAL NEMATODE (GIN) PARASITES ARE COMMON AND SERIOUS INFECTIOUS PARASITES OF LIVESTOCK. GIN INFECTIONS HAVE SERIOUS HEALTH AND PRODUCTION CONSEQUENCES AND INCLUDE MANIFESTATIONS SUCH AS DIARRHEA, LETHARGY, WEIGHT LOSS AND GROWTH STUNTING, MEAT/WOOL/MILK PRODUCTION LOSS, REDUCED REPRODUCTIVE RATES, AND COLIC MANIFESTATIONS. ROUTINE DEWORMING IS A MAINSTAY IN LIVESTOCK PRACTICE. HOWEVER, PARASITE RESISTANCE TO ALL DEWORMING DRUGS (ANTHELMINTICS) IS RAMPANT, AND NEW ANTHELMINTICS ARE URGENTLY NEEDED. THIS PROJECT PROPOSES A NEW APPROACH FOR DEWORMING--A PARAPROBIOTIC THAT EXPRESSES VERTEBRATE-SAFE PROTEINS, CRY5B AND/OR CRY14A, WITH ACTIVITY AGAINST NEMATODES. CRY5B AND CRY14A ARE CRYSTAL (CRY) PROTEINS PRODUCED BY THE BACTERIUM BACILLUS THURINGIENSIS. CRY5B HAS DEMONSTRATED ACTIVITY AGAINST STRONGYLID PARASITES OF SHEEP IN VIVO AND HORSES IN VITRO AND CRY14A IS HIGHLY ACTIVE IN VITRO AGAINST DEVELOPING LARVAL STAGES OF KEY PARASITES. THE AIMS OF THIS PROJECT ARE (1) PRODUCE AND TEST IN FISTULATED ANIMALS NEW FORMULATIONS TO PROTECT THE PARAPROBIOTIC FROM PREMATURE DEGRADATION; (2) COMPARE THE EFFICACY OF FORMULATED CRY5B AND CRY14A AGAINST KEY PARASITES OF SHEEP (RUMINANTS) AND HORSES (MONOGASTRICS); AND (3) PERFORM DOSE-RESPONSE STUDIES OF THE BEST THERAPIES IDENTIFIED. AT THE CONCLUSION OF THIS STUDY, OUR GOAL IS TO HAVE OPTIMIZED A NEW POTENT AND COMMERCIALLY VIABLE FORMULATED ANTHELMINTIC THERAPY WITH BROAD ACTIVITY AGAINST GIN PARASITES OF FARM ANIMALS

$646,000FY2021National Institute of Food and AgricultureUSDA

University Of Rhode Island, Kingston RI

Investigators

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**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** GASTROINTESTINAL NEMATODE (GIN) PARASITES ARE COMMON AND SERIOUS INFECTIOUS PARASITES OF LIVESTOCK. GIN INFECTIONS HAVE SERIOUS HEALTH AND PRODUCTION CONSEQUENCES AND INCLUDE MANIFESTATIONS SUCH AS DIARRHEA, LETHARGY, WEIGHT LOSS AND GROWTH STUNTING, MEAT/WOOL/MILK PRODUCTION LOSS, REDUCED REPRODUCTIVE RATES, AND COLIC MANIFESTATIONS. ROUTINE DEWORMING IS A MAINSTAY IN LIVESTOCK PRACTICE. HOWEVER, PARASITE RESISTANCE TO ALL DEWORMING DRUGS (ANTHELMINTICS) IS RAMPANT, AND NEW ANTHELMINTICS ARE URGENTLY NEEDED. THIS PROJECT PROPOSES A NEW APPROACH FOR DEWORMING--A PARAPROBIOTIC THAT EXPRESSES VERTEBRATE-SAFE PROTEINS, CRY5B AND/OR CRY14A, WITH ACTIVITY AGAINST NEMATODES. CRY5B AND CRY14A ARE CRYSTAL (CRY) PROTEINS PRODUCED BY THE BACTERIUM BACILLUS THURINGIENSIS. CRY5B HAS DEMONSTRATED ACTIVITY AGAINST STRONGYLID PARASITES OF SHEEP IN VIVO AND HORSES IN VITRO AND CRY14A IS HIGHLY ACTIVE IN VITRO AGAINST DEVELOPING LARVAL STAGES OF KEY PARASITES. THE AIMS OF THIS PROJECT ARE (1) PRODUCE AND TEST IN FISTULATED ANIMALS NEW FORMULATIONS TO PROTECT THE PARAPROBIOTIC FROM PREMATURE DEGRADATION; (2) COMPARE THE EFFICACY OF FORMULATED CRY5B AND CRY14A AGAINST KEY PARASITES OF SHEEP (RUMINANTS) AND HORSES (MONOGASTRICS); AND (3) PERFORM DOSE-RESPONSE STUDIES OF THE BEST THERAPIES IDENTIFIED. AT THE CONCLUSION OF THIS STUDY, OUR GOAL IS TO HAVE OPTIMIZED A NEW POTENT AND COMMERCIALLY VIABLE FORMULATED ANTHELMINTIC THERAPY WITH BROAD ACTIVITY AGAINST GIN PARASITES OF FARM ANIMALS · GrantIndex