Prophylactic effect of bacteriophages on mice subjected to chemotherapy-induced immunosuppression and bone marrow transplant upon infection with Staphylococcus aureus

Abstract

Due to the increased resistance of bacteria to antibiotics, phage therapy may be an alternative to treat or prevent suppurative infections in immunocompromised patients. The authors' recent studies indicated that such an approach is particularly beneficial in immunosuppressed mice. A5/L bacteriophages, specific for the Staphylococcus aureus strain L, were tested for their ability to protect CBA mice subjected to myeloablative (busulfan) and immunosuppressive (cyclophosphamide) conditioning followed by a syngeneic bone marrow transplantation (BMT) and infected with a sublethal or lethal dose of bacteria. The application of phages to immunocompromised mice given BMT led to a significant (>90%) reduction in bacterial load in the spleen and liver. Moreover, 72% of such mice attained long-term survival versus 8.2% survival of mice not treated with phages. Analysis of leukocyte number and blood cell type composition revealed that phage application increased the leukocyte numbers and neutrophil content in the circulating blood. Moreover, phage application led to an increased content of the myelocytic cell lineage in the bone marrow. The protective effects of phages in immunosuppressed mice are both direct (bacteriolytic) and indirect (by stimulation of myelopoiesis). The results suggest a potential benefit of phage therapy in immunocompromised patients subjected to bone marrow transplant procedures.