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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/22501

Title: A proposed integrated approach for the preclinical evaluation ofphage therapy in Pseudomonas infections
Authors: Danis-Wlodarczyk, K.
Vandenheuvel, D.
Jang, H.B.
Briers, Y.
Olszak, T.
Arabski, M.
Wasik, S.
Drabik, M.
Higgins, G.
Tyrrell, J.
Harvey, B.J.
Noben, Jean-Paul
Lavigne, R.
Drulis-Kawa, Z.
Issue Date: 2016
Citation: Scientific Reports, 6, (Art N° 28115)
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 (279,593bp 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.
URI: http://hdl.handle.net/1942/22501
DOI: 10.1038/srep28115
ISSN: 2045-2322
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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