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Sci Rep. 2016 Jun 15;6:28115. doi: 10.1038/srep28115.

A proposed integrated approach for the preclinical evaluation of phage therapy in Pseudomonas infections.

Author information

1
Department of Pathogen Biology and Immunology, Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland.
2
Laboratory of Gene Technology, KULeuven, Leuven, Belgium.
3
Laboratory of Applied Biotechnology, Department of Applied Biosciences, Ghent University, Ghent, Belgium.
4
Department of Microbiology, Institute of Biology, The Jan Kochanowski University in Kielce, Kielce, Poland.
5
Department of Molecular Physics, Institute of Physics, The Jan Kochanowski University in Kielce, Kielce, Poland.
6
Department of Astrophysics, Institute of Physics, The Jan Kochanowski University in Kielce, Kielce, Poland.
7
National Children Research Centre, Dublin, Ireland.
8
Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
9
Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Hasselt University, Diepenbeek, Belgium.

Abstract

Bacteriophage therapy is currently resurging as a potential complement/alternative to antibiotic treatment. However, preclinical evaluation lacks streamlined approaches. We here focus on preclinical approaches which have been implemented to assess bacteriophage efficacy against Pseudomonas biofilms and infections. Laser interferometry and profilometry were applied to measure biofilm matrix permeability and surface geometry changes, respectively. These biophysical approaches were combined with an advanced Airway Surface Liquid infection model, which mimics in vitro the normal and CF lung environments, and an in vivo Galleria larvae model. These assays have been implemented to analyze KTN4 (279,593 bp dsDNA genome), a type-IV pili dependent, giant phage resembling phiKZ. Upon contact, KTN4 immediately disrupts the P. aeruginosa PAO1 biofilm and reduces pyocyanin and siderophore production. The gentamicin exclusion assay on NuLi-1 and CuFi-1 cell lines revealed the decrease of extracellular bacterial load between 4 and 7 logs and successfully prevents wild-type Pseudomonas internalization into CF epithelial cells. These properties and the significant rescue of Galleria larvae indicate that giant KTN4 phage is a suitable candidate for in vivo phage therapy evaluation for lung infection applications.

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