The virulent bacteriophage Henu8 as an antimicrobial synergist against Escherichia coli

As the overuse of antibiotics has not yet been strictly limited in urban areas, drug-resistant Escherichia coli has become a fatal pressure for bacteremia treatment. Considering the outstanding performance of bacteriophages in vitro, bacteriophages may serve as an alternative to heal chronic refractory infections. In this study, a 49,890 bp double-stranded circular DNA phage, Henu8, was isolated and was able to lyse the group of E. coli strains tested in this study. Prominent biological characterization revealed that the highly adsorbed bacteriophage Henu8 could form a fully transparent plaque with a narrow translucent halo. The optimal multiplicity of infection of the bacteriophage Henu8 was 0.01, with a burst size of 275 PFU/cell. Genomic analysis revealed a G + C content of 44.17% Henu8, in which 65 open reading frames were located, which could be assigned as a new species in the genus Hanrivervirus of the subfamily Tempevirinae. The effective antibacterial ability and the obvious biofilm destruction and inhibition capability of phage Henu8 were observed. The time-killing assay demonstrated the synergetic potential of Henu8 with antibiotics in vitro for E. coli eradication. Henu8 has profound medicinal potential in a mouse bacteremia model. These studies indicate that Henu8 is a novel bacteriophage with therapeutic potential alone or in combination with antibiotics for clinical treatment.IMPORTANCEThe findings described in this study constitute concrete evidence that it is possible to significantly synergize the antimicrobial activity of bacteriophages and antibiotics. We showed that the newly isolated potent bacteriophage Henu8 lyses Escherichia coli rapidly but tends to produce resistant bacteria. The bacteriophage Henu8 has synergistic antimicrobial effects with several antibiotics and is not susceptible to developing resistance. These results provide further evidence that bacterial resistance to phages arises, possibly at an adaptive cost to sensitivity to antibiotics. Therefore, the findings of this study are important for increasing the potential of phages for clinical applications and developing new approaches to improve their therapeutic efficacy against bacterial drug resistance.