Bacteriophage Therapy of Salmonella enterica: A Fresh Appraisal of Bacteriophage Therapy

Background. The most serious criticisms leveled at bacteriophage therapy are as follows: phages induce neutralizing antibodies, phages are active only when administered shortly after bacterial infection, and phage-resistant bacteria emerge rapidly in the course of therapy. Methods. Phages lytic for several Salmonella enterica serovars were isolated by means of standard protocols from feces of patients with gastroenteritis. Growth of S. enterica serovar Paratyphi B (Salp572(phi 1S)) in the presence of phage phi 1 (selected from among 8 phages for its larger host range) provided a phage phi 1 resistant bacterial strain (Salp572(phi 1R)). The properties of the Salp572(phi 1S) and Salp572(phi 1R) strains and of phage phi 1 were studied in a mouse model of experimental infection. Results. Phages induced nonneutralizing antibodies and were active 2 weeks after experimental infection of mice; phage-resistant bacteria were avirulent and short lived in vivo. More importantly, phage-resistant bacteria were excellent vaccines, protecting against lethal doses of heterologous S. enterica serovars. Conclusions. Phage therapy effectiveness has not yet been properly assessed.