title: Development of expanded host range phage active on biofilms of multi-drug resistantPseudomonas aeruginosa.
abstract: Phage therapy is a promising treatment of multi-drug resistant (MDR) bacterial infections but is limited by the narrow host range of phage. To overcome this limitation, we developed a host range expansion (HRE) protocol that expands the host range ofPseudomonas aeruginosa-specific phage by cycles of co-incubation of phage with multipleP. aeruginosastrains. Application of the HRE protocol to a mixture of 4 phages, using 16P. aeruginosastrains for development, resulted in undefined phage mixtures with greatly expanded host range. Individual phage clones derived from the undefined mixture had expanded host ranges but no individual clone could lyse all of the strains covered by the undefined mixture from which it was isolated. Reconstituting host range-characterized clones into cocktails produced defined cocktails with predictable and broad host ranges. The undefined mixture from the 30thcycle of the mixed-phage HRE (4ϕC30) showed a dose-dependent ability to prevent biofilm formation by, and to reduce a pre-existing biofilm of, 3P. aeruginosaclinical isolates that produced high amounts of biofilm. A defined cocktail reconstituted from 3 host range-characterized clones had activity on high biofilm-formers susceptible to the phage. Phage therapy was superior to antibiotic therapy (levofloxacin) in a strain ofP. aeruginosathat was resistant to levofloxacin. The HRE protocol establishes a rapid approach to create libraries of phage clones and phage cocktails with broad host range, defined composition and anti-biofilm activity.
authors.affiliation: Section of Infectious Diseases, Departments of Medicine and Surgery, Baylor College of Medicine , Houston, TX, USA.
authors.forename: Abigail C
authors.initials: AC
authors.lastname: Mapes
authors.affiliation: Section of Infectious Diseases, Departments of Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA; Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
authors.forename: Barbara W
authors.initials: BW
authors.lastname: Trautner
authors.affiliation: Section of Infectious Diseases, Departments of Medicine and Surgery, Baylor College of Medicine , Houston, TX, USA.
authors.forename: Kershena S
authors.initials: KS
authors.lastname: Liao
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine , Houston, TX, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Ramig
keywords: Bacteriophage; Pseudomonas aeruginosa; biofilm; host range