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ANTIBIOTICS HAVE BEEN USED SUCCESSFULLY TO TREAT BACTERIAL INFECTION IN BOTH HUMANS AND ANIMALS FOR MANY YEARS. IN LIVESTOCK, ANTIBIOTICS ARE USED FOR GROWTH PROMOTION, FEED EFFICIENCY AND VETERINARY MEDICINE. UNFORTUNATELY, EXTENSIVE USE OF ANTIBIOTICS MAY LEAD TO THE PROLIFERATION OF NOVEL ANTIMICROBIAL RESISTANCE MECHANISMS. THIS DIRE SITUATION IS BECOMING A SERIOUS THREAT TO PUBLIC HEALTH, ESPECIALLY SINCE LIVESTOCK CAN ACT AS A RESERVOIR FOR THE RESISTANT BACTERIA TO BE TRANSMITTED TO THE HUMAN POPULATION. ANTIBIOTIC RESISTANCE IS CLAIMING MANY LIVES ANNUALLY AND ALSO COSTING HIGHER HEALTHCARE EXPENDITURE FOR INDIVIDUALS, HEALTHCARE ORGANIZATIONS, AND GOVERNMENTAL BODIES. THEREFORE, THERE IS AN URGENT NEED TO ADDRESS THIS GLOBAL ISSUE WITH THE USE OF ALTERNATIVE THERAPIES THAT CAN ELIMINATE THE RISKS POSED BY ANTIBIOTIC TREATMENTS AT THE PRIMARY PRODUCTION LEVEL.THE AIM OF THIS PROJECT IS TO DEVELOP ALTERNATIVE THERAPIES FOR BACTERIAL TREATMENT THAT HAVE LOWER RISK OF DEVELOPINGDRUG RESISTANCE AND THAT ARE TARGET-SPECIFIC. BACTERIOPHAGES CAN ELIMINATE SPECIFIC PATHOGENIC BACTERIA WITHOUT AFFECTING THE NORMAL, BENEFICIAL INTESTINAL MICROFLORA, BY INFECTING AND LYSING ITS TARGETED HOST DURING THE INFECTION CYCLE. THE SPECIFIC DESTRUCTIVE MECHANISM OF PHAGE THERAPY IS A CLEAR ADVANTAGE OVER TRADITIONAL ANTIBIOTIC TREATMENTS, WHERE THE BENEFICIAL GI MICROFLORA IS AFFECTED. CURRENTLY, ORAL DELIVERY OF PHAGES IN LIVESTOCK ARE INEFFICIENT AS THEY USE A HIGH DOSAGE OF A PHAGE COCKTAIL IN HOPES TO REDUCE SHEDDING OF PATHOGENIC BACTERIA. DURING THE DIGESTIVE PROCESS, THE UNPROTECTED PHAGE ARE SUSCEPTIBLE TO DAMAGE WHICH CAN LEAD TO DECREASE EFFECTIVENESS OF THE THERAPY. THUS, THERE IS A NEED TO DESIGN DELIVERY SYSTEMS THAT ARE ABLE TO PROVIDE A MORE EFFICIENT AND EFFECTIVE MEANS FOR DELIVERY OF PHAGES TO THE GUT, WHICH IS THE MAIN SITE TO CONTROL PATHOGEN SHEDDING. THE PROJECT WILL BE CARRIED OUT IN TWO PARTS:FORMULATE AND FABRICATE DELIVERY SYSTEMS TO PROTECT BACTERIOPHAGES.DETERMINE EXTENDED STORAGE STABILITY AND IN VITRO DELIVERY OF THE ENCAPSULATED BACTERIOPHAGES. THE EFFICACY OF ENCAPSULATED BACTERIOPHAGES WILL BE TESTED USING A SIMULATED IN VITRO GI TRACT. FURTHERMORE, INTERACTIONS BETWEEN THE PHAGE AND TARGETED PATHOGEN IN THE GUT WILL BE STUDIED USING A IN VITRO BIOREACTOR THAT SIMULATES THE GUT MICROBIOTA.THE COMPLETION OF THIS PROJECT SHOULD GENERATE RESULTS THAT WOULD FACILITATE SAFE MANUFACTURING OF ENCAPSULATED BACTERIOPHAGES AS ALTERNATIVE THERAPIES I.E., PHAGE THERAPY AS AN ALTERNATIVE TO ANTIBIOTICS, OR THAT ARE CO-ADMINISTERED WITH ANTIBIOTICS. THESE ENCAPSULATED BACTERIOPHAGES WILL BE AN ADVANCEMENT OVER THE CURRENT METHODS OF ORAL ADMINISTRATION OF NAKED PHAGES, WHICH IN THEORY WILL PROVIDE A MORE ECONOMICAL AND EFFICIENT METHOD IN DELIVERING PHAGE TO THE GUT. PHAGE THERAPY COULD THEN BE USED FOR THE EFFECTIVE DECREASE OF PATHOGENIC BACTERIA IN THE GUT BY INCORPORATING THEM INTO FOOD PRODUCTS (E.G., ANIMAL FEEDS AND SPECIAL NEED FOOD PRODUCTS). LASTLY, THE FINDINGS FROM THIS RESEARCH WOULD HELP IMPROVE THE OVERALL SAFETY OF THE FARM TO TABLE CHAIN BY IMPROVING ANIMAL HEALTH AND PRODUCTION.

$165,000FY2019National Institute of Food and AgricultureUSDA

University Of Massachusetts, Amherst MA

Investigators

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