Characterization of a Unique Bordetella bronchiseptica vB_BbrP_BB8 Bacteriophage and Its Application as an Antibacterial Agent

Int J Mol Sci. 2020 Feb 19;21(4):1403. doi: 10.3390/ijms21041403.

Abstract

Bordetella bronchiseptica, an emerging zoonotic pathogen, infects a broad range of mammalian hosts. B. bronchiseptica-associated atrophic rhinitis incurs substantial losses to the pig breeding industry. The true burden of human disease caused by B. bronchiseptica is unknown, but it has been postulated that some hypervirulent B. bronchiseptica isolates may be responsible for undiagnosed respiratory infections in humans. B. bronchiseptica was shown to acquire antibiotic resistance genes from other bacterial genera, especially Escherichia coli. Here, we present a new B. bronchiseptica lytic bacteriophage-vB_BbrP_BB8-of the Podoviridae family, which offers a safe alternative to antibiotic treatment of B. bronchiseptica infections. We explored the phage at the level of genome, physiology, morphology, and infection kinetics. Its therapeutic potential was investigated in biofilms and in an in vivo Galleria mellonella model, both of which mimic the natural environment of infection. The BB8 is a unique phage with a genome structure resembling that of T7-like phages. Its latent period is 75 ± 5 min and its burst size is 88 ± 10 phages. The BB8 infection causes complete lysis of B. bronchiseptica cultures irrespective of the MOI used. The phage efficiently removes bacterial biofilm and prevents the lethality induced by B. bronchiseptica in G. mellonella honeycomb moth larvae.

Keywords: Galleria mellonella; animal model; antibiotic resistance; atrophic rhinitis; biofilm; emerging diseases; phage stability; phage therapy; veterinary microbiology; zoonosis.

MeSH terms

  • Animals
  • Biofilms
  • Bordetella Infections / therapy
  • Bordetella Infections / veterinary*
  • Bordetella bronchiseptica / pathogenicity*
  • Bordetella bronchiseptica / ultrastructure
  • Bordetella bronchiseptica / virology*
  • Host Microbial Interactions
  • Hydrogen-Ion Concentration
  • Larva / microbiology
  • Lepidoptera / microbiology
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Phylogeny
  • Podoviridae / genetics*
  • Podoviridae / growth & development
  • Podoviridae / radiation effects
  • Podoviridae / ultrastructure
  • Temperature
  • Virion / isolation & purification
  • Virion / ultrastructure