The present invention features therapeutic bacteriophage deficient in the lysin protein ("Lys minus" phage). Lys minus bacteriophage are incapable of facilitating efficient lysis of the bacterial host since the enzymatic activity of the lysin of the phage is needed for breaking down the peptidoglycan layer of the bacterial cell wall. Lys minus bacteriophage retain activity in invasion of its appropriate bacterial host, destruction of the bacterial genome, and replication, which are sufficient to inhibit bacterial growth and replication. Therefore, the therapeutic Lys minus phage stops the spread of infection by the bacterial pathogen without lysis of the bacterium. This approach is attractive as it also prevents the release of the phage progeny, thus reducing or eliminating the potential for generation of immune responses against the phage. The incapacitated bacterial pathogen is then removed by the normal defense systems such as phagocytes and macrophages.
