Efficacy of a phage cocktail in controlling phage resistance development in multidrug resistant Acinetobacter baumannii

The control and treatment of multidrug resistant pathogens infections has become a grand challenge for clinicians worldwide. Virulent phage has long been considered as an effective bactericidal agent, which may be a potentially alternative to antibiotics. However, the rapid development of phage resistance seriously hinders the wide and continuous application of virulent phages. In this study, Acinetobacter baumannii phage vB_AbaS_DO was isolated, characterized and used to control the phage resistance development in bacterial strains. Transmission electron microscopy analysis of vBAbaS_D0 indicated it belonged to the Siphoviridae family with an icosahedral head. Its whole genome was 43, 051 bp in size, with a GC content of 45.48% and 55 putative open reading frames. The data showed that vB_AbaS_DO was a virulent phage. Although vB_AbaS_DO had a very weak bactericidal activity, a wide range of Acinetobacter baumannii strains were sensitive to it. The results suggested that the cocktail of vB_AbaS_D0 and another Acinetobacter baumannii phage vB_AbaP_D2 could improve the therapeutic efficacy in vivo and in vitro. The resistance mutation frequency of A. baumannii cells infected with DO or phage cocktail was significantly lower than cells treated with D2 (P < 0.01). Phage therapy in the murine bacteremia model results showed that the percentage of phage resistant mutant occurrence in the phage DO or cocktail treatment group was significantly lower than in phage D2 treatment group (P < 0.01).