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

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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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MLA
Danis-Wlodarczyk, Katarzyna et al. “A Proposed Integrated Approach for the Preclinical Evaluation of Phage Therapy in Pseudomonas Infections.” SCIENTIFIC REPORTS 6 (2016): n. pag. Print.
APA
Danis-Wlodarczyk, K., Vandenheuvel, D., Jang, H. B., Briers, Y., Olszak, T., Arabski, M., Wasik, S., et al. (2016). A proposed integrated approach for the preclinical evaluation of phage therapy in Pseudomonas infections. SCIENTIFIC REPORTS, 6.
Chicago author-date
Danis-Wlodarczyk, Katarzyna, Dieter Vandenheuvel, Ho Bing Jang, Yves Briers, Tomasz Olszak, Michal Arabski, Slawomir Wasik, et al. 2016. “A Proposed Integrated Approach for the Preclinical Evaluation of Phage Therapy in Pseudomonas Infections.” Scientific Reports 6.
Chicago author-date (all authors)
Danis-Wlodarczyk, Katarzyna, Dieter Vandenheuvel, Ho Bing Jang, Yves Briers, Tomasz Olszak, Michal Arabski, Slawomir Wasik, Marcin Drabik, Gerard Higgins, Jean Tyrrell, Brian J Harvey, Jean-Paul Noben, Rob Lavigne, and Zuzanna Drulis-Kawa. 2016. “A Proposed Integrated Approach for the Preclinical Evaluation of Phage Therapy in Pseudomonas Infections.” Scientific Reports 6.
Vancouver
1.
Danis-Wlodarczyk K, Vandenheuvel D, Jang HB, Briers Y, Olszak T, Arabski M, et al. A proposed integrated approach for the preclinical evaluation of phage therapy in Pseudomonas infections. SCIENTIFIC REPORTS. 2016;6.
IEEE
[1]
K. Danis-Wlodarczyk et al., “A proposed integrated approach for the preclinical evaluation of phage therapy in Pseudomonas infections,” SCIENTIFIC REPORTS, vol. 6, 2016.
@article{8043889,
  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.},
  articleno    = {28115},
  author       = {Danis-Wlodarczyk, Katarzyna and Vandenheuvel, Dieter and Jang, Ho Bing and Briers, Yves and Olszak, Tomasz and Arabski, Michal and Wasik, Slawomir and Drabik, Marcin and Higgins, Gerard and Tyrrell, Jean and Harvey, Brian J and Noben, Jean-Paul and Lavigne, Rob and Drulis-Kawa, Zuzanna},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  language     = {eng},
  pages        = {13},
  title        = {A proposed integrated approach for the preclinical evaluation of phage therapy in Pseudomonas infections},
  url          = {http://dx.doi.org/10.1038/srep28115},
  volume       = {6},
  year         = {2016},
}

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