Abstract: Live biotherapeutic compositions and methods are provided for treatment, prevention, or prevention of recurrence of skin and soft tissue infections, such as mastitis and/or intramammary infections, for example, in cows, goats, sows, and sheep. Methods include decolonizing and durably replacing with a live biotherapeutic composition comprising a synthetic microorganism that may safely and durably replace an undesirable microorganism under dermal, mucosal, or intramammary conditions.