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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/22717

Title: A proposed integrated approach for the preclinical evaluation of phage therapy in Pseudomonas infections
Authors: Danis-Wlodarczyk, Katarzyna
Vandenheuvel, Dieter
Bin Jang, Ho
Briers, Yves
Olszak, Tomasz
Arabski, Michal
Wasik, Slawomir
Drabik, Marcin
Higgins, Gerard
Tyrrell, Jean
Harvey, Brian J.
Noben, Jean-Paul
Lavigne, Rob
Drulis-Kawa, Zuzanna
Issue Date: 2016
Citation: SCIENTIFIC REPORTS, 6, p. 1-13 (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 (279,593 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.
Notes: [Danis-Wlodarczyk, Katarzyna; Olszak, Tomasz; Drulis-Kawa, Zuzanna] Univ Wroclaw, Inst Genet & Microbiol, Dept Pathogen Biol & Immunol, Wroclaw, Poland. [Danis-Wlodarczyk, Katarzyna; Vandenheuvel, Dieter; Bin Jang, Ho; Briers, Yves; Lavigne, Rob] KULeuven, Lab Gene Technol, Leuven, Belgium. [Briers, Yves] Univ Ghent, Dept Appl Biosci, Lab Appl Biotechnol, Ghent, Belgium. [Arabski, Michal] Jan Kochanowski Univ Humanities & Sci, Inst Biol, Dept Microbiol, Kielce, Poland. [Wasik, Slawomir] Jan Kochanowski Univ Humanities & Sci, Inst Phys, Dept Mol Phys, Kielce, Poland. [Drabik, Marcin] Jan Kochanowski Univ Humanities & Sci, Inst Phys, Dept Astrophys, Kielce, Poland. [Higgins, Gerard] Natl Children Res Ctr, Dublin, Ireland. [Higgins, Gerard; Tyrrell, Jean; Harvey, Brian J.] Beaumont Hosp, Royal Coll Surg Ireland, Dept Mol Med, Educ & Res Ctr, Dublin, Ireland. [Noben, Jean -Paul] Hasselt Univ, Biomed Res Inst, Sch Life Sci, Diepenbeek, Belgium. [Noben, Jean -Paul] Hasselt Univ, Transnat Univ Limburg, Sch Life Sci, Diepenbeek, Belgium.
URI: http://hdl.handle.net/1942/22717
DOI: 10.1038/srep28115
ISI #: 000384608500002
ISSN: 2045-2322
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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