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.