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(phi1S)) in the presence of phage phi1 (selected from among 8 phages for its larger host range) provided a phage phi1-resistant bacterial strain (Salp572(phi1R)). The properties of the Salp572(phi1S) and Salp572(phi1R) strains and of phage phi1 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.