MASTITIS, DEFINED AS AN INFLAMMATION OF THE MAMMARY GLAND, IS THE MOST COMMON AND MOST ECONOMICALLY SIGNIFICANT DISEASE AFFECTING DAIRY CATTLE. IT IS THE LEADING CAUSE OF ANTIMICROBIAL USE ON DAIRY FARMS. STREPTOCOCCUS UBERIS (S. UBERIS) IS THE MOST PREVALENT GRM-POSITIVE ENVIRONMENTAL PATHOGEN ASSOCIATED WITH MASTITIS AND STRAIN 0140J IS CONSIDERED THE MOST VIRULENT. THE MAJORITY OF DISEASE (~70%) OCCURS AROUND THE TIME OF PARTURITION. CONTROL PRACTICES FOR MASTITIS, INCLUDING SANITARY REARING, HOUSING AND MILKING ENVIRONMENTS, AND TEAT DISINFECTION ARE LESS EFFECTIVE FOR CONTROLLING S. UBERIS-ASSOCIATED MASTITIS THAN OTHER MASTITIS PATHOGENS. AS A CONSEQUENCE, INTRAMAMMARY (IM) INFECTIONS CAUSED BY S. UBERIS ARE ESCALATING EVEN FOR WELL-MANAGED HERDS. STREPTOCOCCUS UBERIS -ASSOCIATED MASTITIS IS AN IMPORTANT ANIMAL WELFARE ISSUE BECAUSE OF THE SUFFERING IT CAUSES TO DAIRY COWS VIA A DECREASE MILK PRODUCTION AND FEED INTAKE, SWELLING OF THE UDDER, AND, IN EXTREME CASES, SEPTICEMIA ORENDOTOXEMIA CAUSED BY MASTITIS CAN RESULT IN DEATH. IT ALSO RESULTS IN VERY HIGH ECONOMIC LOSSES TO AFFECTED PRODUCERS EXCEEDING $2 BILLION PER YEAR COSTING APPROXIMATELY $179 PER CLINICAL CASE. GROWING CONSUMER CONCERNS REGARDING THE POTENTIAL FOR ANTIMICROBIAL RESISTANCE HAVE LED TO THE EXAMINATION OF ALTERNATIVE STRATEGIES FOR CONTROLLING MASTITIS WHILE REDUCING THE USE OF ANTIBIOTICS ON-FARM. THE STREPTOCOCCAL C1 PHAGE LYSIN, PLYC, IS THE MOST POTENT BACTERIOPHAGE ENDOLYSIN DESCRIBED TO DATE. THIS STUDY ADDRESSES THE USE OF A BACTERIOPHAGE ENZYME, PLYC, AS A NON-ANTIBIOTIC ALTERNATIVE THERAPY FOR THE TREATMENT OF S. UBERIS MASTITIS TO REDUCE USE OF ANTIBIOTICS, IMPROVE ANIMAL WELFARE AND ECONOMIC OUTCOME FOR PRODUCERS, MINIMIZE THE RISK OF ANTIBIOTIC RESIDUES IN MILK, AMELIORATE EFFECTIVENESS OF THERAPY WHEN USED IN COMBINATION WITH ON-FARM CULTURE SYSTEMS AND PROVIDE A NEW TREATMENT STRATEGY FOR CONVENTIONAL DAIRY PRODUCERS AS WELL AS ORGANICALLY MANAGED FARMS WHERE ANTIBIOTIC USAGE IS BANNED AND TREATMENT OPTIONS ARE LIMITED.THE SPECIFIC SCIENTIFIC OBJECTIVES OF THIS PROPOSAL ARE DESIGNED TO 1) EXAMINE THE USE OF PLYC, A BACTERIOPHAGE ENDOLYSIN, AS A NEW IM THERAPEUTIC FOR S. UBERIS MASTITIS IN LACTATING DAIRY COWS, 2) IDENTIFY APPROPRIATE WITHDRAWAL TIMES MILK FOR PLYC, AND 3) ELUCIDATE PRE-CLINICAL FACTORS SUCH AS THE BACTERIOLYTIC MECHANISM OF PLYC AGAINST S. UBERIS, ANTI-BIOFILM PROPERTIES AND RESISTANCE DEVELOPMENT. FOR OBJECTIVES 1 AND 2, THIRTEEN (N = 8 QUARTERS/TREATMENT; 25% REPLACEMENTS) HOLSTEIN-FRIESIAN LACTATING DAIRY COWS WILL BE INOCULATED 500 CFU OF S. UBERIS (STRAIN 0140J) INTO ALL FOUR MAMMARY QUARTERS. AFTER INFECTION IS ESTABLISHED, QUARTERS WITHIN COW (N = 8/TREATMENT) WILL BE RANDOMLY ASSIGNED TO RECEIVE 0, 62.5, 125 AND 250 MG OF PLYC OR CEFTIOFUR HYDROCHLORIDE (I.E. 125 MG X 10 ML VOLUME OF SPECTRAMAST® LC, ; A COMMON INTRAMAMMARY ANTIBIOTIC USED IN THE DAIRY INDUSTRY) ONCE DAILY FOR 3 CONSECUTIVE DAYS. ASEPTIC QUARTER FOREMILK SAMPLES WILL BE COLLECTED FOR 30 DAYS TO ASSESS CURE RATES. NUMBER OF CURES AND NUMBER OF CLEAR MILKINGS THAT A QUARTER REMAINED FREE OF S. UBERIS WILL BE RECORDED. FOR OBJECTIVE 3, THE MINIMAL BIOFILM ERADICATION CONCENTRATION, THE BIOMASS ERADICATION, THE MECHANISM OF PLYC ACTION AND THE DEVELOPMENT OF RESISTANCE WILL BE ASSESSED IN VITRO. THIS PROPOSAL INVOLVES THERAPEUTIC INTERVENTIONS FOR TREATMENT OF BOVINE MASTITIS EXAMINING NON-ANTIBIOTIC ALTERNATIVES.

University Of Maryland, College Park, College Park MD

Investigators